Find information on thousands of medical conditions and prescription drugs.


|} Carbachol (Kar-ba-kol ), also known as carbamylcholine (sold under the brand names Carbastat&reg:, Carboptic&reg:, Isopto Carbachol&reg:, Miostat), is classified as a cholinergic. It is primarily used in the treatment of glaucoma, but is also used during ophthalmic surgery. In most countries it is only available by prescription. Carbachol eyedrops are used to decrease the pressure in the eye for people with glaucoma. It is sometimes used to constrict the pupils during cataract surgery. more...

Calcium folinate
Chenodeoxycholic acid
Choriogonadotropin alfa
Chorionic gonadotropin
Clavulanic acid

In the cat and rat, carbachol is well-known for its ability to induce rapid eye movement (REM) sleep when microinjected into the pontine reticular formation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic receptors (mAChRs).

Clinical Info

Chemistry and pharmacokinetics

Carbachol is a choline ester and a positively charged quaternary ammonium compound. It is not well absorbed in the gastro-intestinal tract and does not cross the blood-brain barrier. It is usually administered topical ocular or through intraocular injection. Carbachol is not easily metabolized by cholinesterase, its duration of action is 4 to 8 hours with topical administration and 24 hours for intraocular administration. Since carbachol is poorly absorbed through topical administration, benzalkonium chloride is mixed in to promote absorption.

Mechanisms of action

Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors. In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.


Topical occular administration is used to decrease intraocular pressure in people with primary open-angle glaucoma. Intraocular administration is used to produce miosis after lens implantation during cataract surgery. Carbachol can also be used to stimulate bladder emptying if the normal emptying mechanism is not working properly.

Contraindications and precautions

Use of carbachol, as well as all other muscarinic receptor agonists, is contraindicated in patients with asthma, coronary insufficiency, gastroduodenal ulcers, and incontinence. The parasympathomimetic action of this drug will exacerbate the symptoms of these disorders.



  • Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
  • Canadian Pharmacists Association (2000). Compendium of pharmaceuticals and specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
  • Carbachol (1998). MedlinePlus. Retrieved June 27, 2004, from
  • Carbachol (2003). RxList. Retrieved June 27, 2004, from
  • National Institute for Occupational Safety and Health. (2002). Choline, chloride, carbamate. In The registry of toxic effects of chemical substances. Retrieved June 27, 2004, from
  • Carbachol Chloride (2004). Hazardous Substances Data Bank. Retrieved July 16, 2004, from


[List your site here Free!]

Short-Term Cigarette Smoke Exposure Enhances Allergic Airway Inflammation in Mice
From American Journal of Respiratory and Critical Care Medicine, 7/15/05 by Moerloose, Katrien B

Rationale: Epidemiologic studies suggest that tobacco smoke contributes to the prevalence and occurrence of exacerbations in asthma. The effect of active smoking in adolescents with atopy is poorly understood. Objectives: We developed an experimental model to investigate the influence of smoking on antigen-induced airway inflammation and airway responsiveness in mice that were previously sensitized. Methods: Ovalbumin (OVA)-sensitized BALB/c mice were exposed to air or mainstream smoke (5 days/week) and to phosphate-buffered saline (PBS) or OVA aerosol (3 times/week) for 2 weeks (n = 8 for each group). Results: Airway responsiveness to intravenously injected carbachol was increased (p

Keywords: additive; asthma; cytokines; hyperresponsiveness; severity

Epidemiologic studies indicate that airway pollutants, such as tobacco smoke, contribute to the development and the increase in the severity of asthma. Active as well as passive smoking is positively associated with asthma severity (1-9). Exposure to cigarette smoke results in more frequent asthma attacks, more asthma symptoms (1), a lower lung function (2), an accelerated decline in lung function (2, 3), and higher asthma severity scores (4). Moreover, active cigarette smoking impairs the efficacy of short-term inhaled corticosteroid treatment in steroid-naive patients with asthma (5) and the efficacy of oral corticosteroids in patients with chronic stable asthma (6). The severity of asthma is strongly correlated with current smoking (7), and some studies suggest that there is an increased risk for bronchial asthma in persons who have smoked for 3 years or more (8). Adolescents who start smoking might thus be at increased risk for the development of asthma. Little is known about the effect of active smoking in adolescents already sensitized to an allergen. In some epidemiologic studies that assessed the effect of the interaction between smoking and atopy on asthmalike symptoms (9-11), atopy and smoking were found to be independent risk factors for the development of asthma during adolescence. To understand the inflammatory mechanisms involved in young adults with atopy who start smoking, we developed an experimental model. In this model, the influence of smoking on airway inflammation and airway responsiveness in BALB/c mice that were previously sensitized was investigated.

Some of the results of these studies have been previously reported in the form of an abstract (12).



Male inbred BALB/c mice of about 8 weeks old were obtained from Harlan CBP (Zeist, the Netherlands).


All mice were immunized by an intraperitoneal injection of 10 μg ovalbumin (OVA) adsorbed to 1 mg aluminum hydroxide on Day O and boosted on Day 7.

In Vivo Tobacco Smoke Exposure

Mainstream cigarette smoke exposures were performed four times a day, 5 days a week, with five Kentucky Reference cigarettes (1R3) per five mice per exposure. Details are provided in the online supplement.

OVA Exposure and Experimental Protocol

Air or smoke exposures took place 5 days a week from Day 14 until Day 24. At Days 14, 16, 18, 21, and 24 (30 minutes after air or smoke exposure) mice were exposed to OVA (1%) (details provided online) or phosphate-buffered saline (PBS) aerosol during 30 minutes (n = 8 in each group).

Assessment of Airway Responsiveness

Airway responsiveness to carbachol was measured 24 hours after the final allergen exposure. More details are provided in the online supplement. Lung resistance, induced by increasing doses of carbachol, was evaluated with a computerized pulmonary mechanics analyzer (Mumed lung function recording system, version 5.0; Mumed Systems Ltd., London, UK). The concentration of carbachol causing a 50% increase of baseline resistance was calculated.

Bronchoalveolar Lavage and Lung Digest

Immediately after the assessment of airway responsiveness, bronchoalveolar lavage (BAL) was performed via intratracheal instillation of 1 ml Hank's balanced salt solution (Pasteur, Brussels, Belgium) plus 1% bovine serum albumin for cytokine measurements. Three instillations with 1 ml of Hank's balanced salt solution were performed to collect cells for total and differential (cytospin analysis) cell counts. The remaining cells and cells from lung digest were analyzed by fluorescence activated cell sorter. (See online supplement for details.)

Measurement of Total and OVA-specific IgE

Blood was drawn from the heart for measurement of total and OVA-specific IgE with ELISA. (See online supplement for details.)

Immunofluorescent Labeling and Flow Cytometry

Flow cytometry data were acquired on a FACSVantage SE flow cytometer running CELLQuest 3.0 software (Becton Dickinson, San Jose, CA). FlowJo software (Treestar, San Carlos, CA) was used for data analysis. (See online supplement for details.)

Cytokine and Chemokine Measurements

Measurements have been performed on supernatant of lavage fluid. Interleukin 5 (IL-5) was measured with a sensitive bioassay with a detection limit at approximately 5 pg/ml, as previously described (13). Eotaxin (sensitivity, 3 pg/ml), IFN-γ (sensitivity, 2 pg/ml), thymus- and activation-regulated chemokine (TARC; sensitivity,

Statistical Analysis

Reported values were expressed as mean ± SEM, and p values of less then 0.05 were regarded as significant. For the statistical analysis, the SPSS program was used (SPSS 11.0; SPSS, Inc., Chicago, IL). All outcome variables were compared using nonparametric tests (Kruskal-Wallis, Mann-Whitney U test with Bonferroni's corrections). (See online supplement for details.)

For measurements of bronchial responsiveness, cumulative dose-response curves for the changes in lung resistance with increasing doses of carbachol were constructed. The changes in lung resistance were expressed as percentage increase in lung resistance. The cumulative dose-response curves were compared through analysis of variance with post hoc (least significant difference and Scheffé) tests.


BAL Fluid

BAL fluid (BALF) of immunized mice exposed to cigarette smoke or aerosolized OVA contained an increased amount of cells compared with air- and PBS-exposed immunized animals as indicated in Table 1. Combined exposure to cigarette smoke and OVA aerosol had an additive effect on total cell number in BALF.

OVA exposure increased the number of eosinophils in BALF, whereas cigarette smoke exposure increased the number of neutrophils in BALF (Table 1).

Smoke or OVA exposure as such did not increase the number of macrophages in BALF. Cigarette smoke synergized with OVA to significantly elevate the total number of macrophages in BALF (p

The number of dendritic cells (DCs) in BALF was increased after exposure to either cigarette smoke or OVA. Exposure to both stimuli further increased the amount of DCs recovered from BALF (Table 1).

Measurement of Total and OVA-specific IgE

Total IgE in serum was not increased because of exposure to cigarette smoke as such. In mice challenged with OVA, a significant increase in total IgE was observed (Table 2).

OVA-specific IgE was significantly higher in mice exposed to OVA compared with PBS-exposed mice. The further increase observed in the group that was simultaneously exposed to OVA and cigarette smoke came close to formal significance (p = 0.06; Table 2).

Lung Tissue: Fluorescence-activated Cell Sorter Analysis

There were no significant differences in total cell numbers in lung tissue between the four groups (data not shown), although some shifts were seen in cell lineages: DCs and activated CD4^sup +^ and CD8^sup +^ T lymphocytes (Figure 1) were increased by exposure to either cigarette smoke or OVA. Simultaneous smoke and OVA exposure had an additive effect on the three cell types.

Airway Responsiveness

Figure 2 shows the percentage of increase in lung resistance with increasing doses of carbachol. After 2 weeks of cigarette smoke or OVA exposure, the dose-response curve for carbachol was not significantly different from those of control animals. In the group exposed to both OVA and cigarette smoke, airway responsiveness significantly increased compared with all other groups.

Cytokine and Chemokine Measurements in BALF Supernatant

IL-5, IFN-γ, and tumor necrosis factor α were not detectable in the supernatant of BALF. Eotaxin was significantly increased (p

Exposure to OVA increased IL-13 in BALF supernatant (p


This study examined the effect of concurrent exposure to allergen and cigarette smoke in a murine model of allergic airway inflammation. As expected, immunized BALB/c mice challenged with OVA developed an eosinophilic airway inflammation, which was associated with increased numbers of lymphocytes and DCs in lavage and lung tissue. Exposure of mice to cigarette smoke induced a neutrophilic influx. Sensitized mice exposed to both OVA and cigarette smoke were found to have a pulmonary inflammation with characteristics of both smoke- and allergeninduced inflammation. OVA-specific IgE in serum as well as Th2-cytokine levels in BALF supernatant were increased when OVA and cigarette smoke exposure were combined. These changes were associated with increased airway responsiveness.

It is well documented that cigarette smoking causes an accumulation of neutrophils and macrophages in human lung tissue (14-16) and BALF (17). Neutrophils in BALF were also increased in our model with exposure of mice to mainstream smoke. In a study by Chalmers and others (18), total sputum cell counts were higher in smokers with asthma than in healthy nonsmokers, healthy smokers, and nonsmokers with asthma. The authors suggested that the neutrophilic inflammation related to smoking may be additive to the underlying asthmatic airway inflammation. Seymour and colleagues (19) used a murine model of allergy to demonstrate that environmental tobacco smoke could amplify an ongoing allergic response (19). In that study, sidestream cigarette smoke was aged and diluted in conditioning chambers for 2 minutes, and then further diluted with fresh air, whereas in our model, mainstream cigarette smoke was used. In a recent report, Melgert and coworkers (20) described an attenuation of OVA-induced airway inflammation when allergic mice were exposed to cigarette smoke. At first sight, the results obtained in this study are contradictory to the results we found. However, these divergent results can be explained by the different experimental design, and thus, in fact, both studies are complementary rather than conflicting. Our study is a model of acute simultaneous exposure of allergen and cigarette smoke over a period of days, whereas Melgert and coworkers (20) used a more chronic model of airway inflammation, in which C57Bl/6j mice were challenged with antigen aerosol for 4 weeks before the exposure to tobacco smoke started. A nose-only exposure of mice to mainstream smoke was used during 3 weeks, resulting in carboxyhemoglobin (HbCO) levels of approximately 22% directly after smoking. It is known that exogenously administered CO attenuates airway inflammation (21) and hyperresponsiveness (22) in mice, and this can explain the suppressive effects Melgert and coworkers (20) observed. In our model, HbCO immediately after smoke exposure was 8.29 ± 1.4% (n = 7), according well with previous reports (23) and with percentage of HbCO in peripheral blood of human smokers (4-10%) (24).

In our model, DCs in BALF and in lung tissue were increased in mice that were exposed to either OVA or cigarette smoke. The further increase in DCs when smoke and OVA were combined suggests that the increase in DCs related to smoking may be additive to the underlying allergic airway inflammation. DCs can secrete chemotactic factors that attract other inflammatory cells, such as neutrophils, macrophages, natural killer cells, and more DCs, and they are also important in the induction and maintenance of eosinophilic airway inflammation (25). Activated CD4^sup +^ and CD8^sup +^ T cells were increased in mice exposed to tobacco smoke, with a predominance of the number of CD4^sup +^ T cells. A similar observation was made in guinea pigs (26). In humans, however, the inflammatory response to tobacco smoke was mostly characterized by increases of CD8^sup +^ T lymphocytes rather than CD4^sup +^ T cells (27). Activated CD4^sup +^ and CD8^sup +^ T cells were increased in lungs of mice that were aerosolized with OVA. In this study, activated CD4^sup +^ T lymphocytes were increased when mice were exposed to both smoke and OVA versus mice exposed to a single stimulus. Other investigators previously showed that an accumulation of activated CD4^sup +^ T lymphocytes was associated with the development of airway hyperresponsiveness (28, 29). It may come as a surprise that OVA exposure as such did not induce hyperresponsiveness, but under the current circumstances, there was no need to obtain a shift in the dose-response curve by exposure to OVA only. On the contrary, our experiments were set up to examine the interaction between OVA and cigarette smoke, and our results indeed show an increase in airway responsiveness when mice are exposed to both OVA and cigarette smoke.

The higher nonspecific airway responsiveness observed in mice exposed to both OVA and smoke could be a functional consequence of the large increase in activated CD4^sup +^ T lymphocytes, secreting a whole range of cytokines. Also, the increased number of eosinophils may help explain this phenomenon, because mediators derived from eosinophils are believed to induce airway hyperresponsiveness (21, 30). Another cell type that plays a role in the development of airway hyperresponsiveness is CD8^sup +^ T lymphocytes (31, 32). In our model, an additive effect was seen on CD8^sup +^ T lymphocytes when smoke and OVA exposure were combined, further explaining the observed lung function data. To further unravel the mechanisms behind our observations, cytokine measurements have been performed on BALF supernatant. When sensitized mice are exposed to allergen, a T-helper 2 (Th2) response was seen. In the present experiment, an increase was seen in TARC, IL-13, and eotaxin in BALF supernatant when mice were sensitized and challenged with OVA. These findings clearly indicate that our model is Th2-driven. TARC was elevated in murine lungs during the allergic inflammation after OVA exposure, as previously described by Kawasaki and coworkers (33). Their results indicated that TARC is a pivotal chemokine for the induction of CD4^sup +^ Th2 lymphocyte and eosinophil infiltration in the airways. In our mice, TARC was also elevated significantly in OVA-exposed mice, but to our surprise, a concurrent exposure to cigarette smoke appeared to have an inhibiting effect. Therefore, in our model, the massive increase in activated CD4^sup +^ T cells in both OVA-and smoke-exposed mice can only be partly explained by an increase in TARC levels, so it is likely that other C-C chemokines, such as eotaxin or RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5, play a more important role in this process (34).

IL-13 was increased in mice exposed to OVA versus PBS-exposed mice. Tobacco smoke exposure did not amplify this response. IL-13 regulates IgE production, eosinophil recruitment, and airway hyperresponsiveness (35), and it is the most potent inducer of eotaxin (36), an eosinophil-selective C-C chemokine produced primarily by respiratory epithelial cells. Eotaxin in BAL supernatant was increased in our OVA-exposed mice, whereas a concurrent exposure to smoke had an adjuvant effect. The increased eotaxin level in BAL supernatant was associated with a marked infiltration of the airways with eosinophils. MacLean and colleagues (37) suggested that eotaxin is one of the molecular links between antigen-specific T-cell activation and the recruitment of eosinophils into the airways. Because eotaxin has been demonstrated to partially regulate eosinophil recruitment during the late-phase response (38), it might be possible that a higher amount of eosinophils still had to arrive into the airways at the moment we killed the mice. Furthermore, it may be possible that the influx of other inflammatory cells into the airways because of smoke exposure causes changes in eosinophil recruitment. Our data indicate that acute concurrent exposure to allergen and mainstream cigarette smoke enhances airway inflammation and airway responsiveness in previously sensitized BALB/c mice. These results support the hypothesis that the development of asthmatic symptoms in young adults with atopy is enhanced by starting active smoking.

Conflict of Interest Statement: K.B.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; R.A.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; C.F.J. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

Acknowledgment: The authors thank Eliane Gastrique, Christelle Snauwaert, Katleen De Saedeleer, An Neesen, Indra De Borle, Marie-Rose Mouton, and Greet Barbier for their technical contribution to this work. They thank Dr. Tania Maes and Jo Leroy for the critical reading of the manuscript, and extend their appreciation to Prof. Dr. Jan Tavernier for the IL-5 bioassays.


1. Althuis MD, Sexton M, Prybylski D. Cigarette smoking and asthma symptom severity among adult asthmatics. J Asthma 1999;36:257-264.

2. James AL, Palmer LJ, Kicic E. Maxwell PS, Lagan SE, Ryan GF, Musk AW. Decline in lung function in the busselton health study: the effects of asthma and cigarette smoking. Am J Respir Crit Care Med 2004; 171:109-114.

3. Lange P, Parner J. Vestbo J, Schnohr P, Jensen G. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med 1998;339:1194-1200.

4. Siroux V, Pin I, Oryszczyn MP, Le Moual N, Kauffmann F. Relationships of active smoking to asthma and asthma severity in the EGEA study: epidemiological study on the genetics and environment of asthma. Eur Respir J 2000;15:470-477.

5. Chalmers GW, Macleod KJ, Little SA, Thomson LJ. McSharry CP. Thomson NC. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax 2002;57:226-230.

6. Chaudhuri R, Livingston E, McMahon AD, Thomson L, Borland W, Thomson NC. Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Respir Crit Care Med 2003;168:1308-1311.

7. Beeh KM, Micke P, Ksoll M. Buhl R. Cigarette smoking, but not sensitization to Alternaria, is associated with severe asthma in urban patients. J Asthma 2001;38:41-49.

8. Flodin U, Jonsson P, Ziegler J, Axelson O. An epidemiologic study of bronchial asthma and smoking. Epidemiology 1995;6:503-505.

9. Sunyer J, Anto JM, Kogevinas M, Soriano JB, Tobias A, Munoz A. Smoking and bronchial responsiveness in nonatopic and atopic young adults. Spanish Group of the European Study of Asthma. Thorax 1997;52:235-238.

10. Toren K, Hermansson BA. Incidence rate of adult-onset asthma in relation to age, sex, atopy and smoking: a Swedish population-based study of 15813 adults. Int J Tuberc Lung Dis 1999;3:192-197.

11. Rasmussen F, Siersted HC, Lambrechtsen J, Hansen HS, Hansen NC. Impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic teenagers. Chest 2000; 117:1330-1335.

12. Moerloose K, Pauwels RA, Joos GF. Short-term cigarette smoke exposure enhances allergen induced airway inflammation and airway responsiveness in mice [abstract]. Am J Respir Crit Care Med 2003;167: A65.

13. Van Ostade X, Schauvliege L, Pattyn E, Verhee A, Vandekerckhove J, Tavernier J. A sensitive and versatile bioassay for ligands that signal through receptor clustering. J Interferon Cytokine Res 2000;20:79-87.

14. Hunninghake GW, Crystal RG. Cigarette smoking and lung destruction: accumulation of neutrophils in the lungs of cigarette smokers. Am Rev Respir Dis 1983;128:833-838.

15. Hoidal JR, Niewoehner DE. Lung phagocyte recruitment and metabolic alterations induced by cigarette smoke in humans and in hamsters. Am Rev Respir Dis 1982;126:548-552.

16. Floreani AA, Rennard SI. The role of cigarette smoke in the pathogenesis of asthma and as a trigger for acute symptoms. Curr Opin Pulm Meet 1999;5:38-46.

17. Kuschner WG, D'Alessandro A, Wong H, Blanc PD. Dose-dependent cigarette smoking-related inflammatory responses in healthy adults. Eur Respir J 1996;9:1989-1994.

18. Chalmers GW, Macleod KJ, Thomson L, Little SA, McSharry C, Thomson NC. Smoking and airway inflammation in patients with mild asthma. Chest 2001;120:1917-1922.

19. Seymour BW, Pinkerton KE, Friebertshauser KE, Coffman RL, Gershwin LJ. Second-hand smoke is an adjuvant for T helper-2 responses in a murine model of allergy. J Immunol 1997;159:6169-6175.

20. Melgert BN, Postma DS, Geerlings M, Luinge MA, Klok PA, Van Der Strate BW, Kerstjens HA, Timens W, Hylkema MN. Short-term smoke exposure attenuates ovalbumin-induced airway inflammation in allergic mice. Am J Respir Cell Mol Biol 2004;30:880-885.

21. Takeda K, Haczku A, Lee JJ, Irvin CG, Gelfand EW. Strain dependence of airway hyperresponsiveness reflects differences in eosinophil localization in the lung. Am J Physiol Lung Cell Mol Physiol 2001;281: L394-L402.

22. Ameredes BT, Otterbein LE, Kohul LK, Gligonic AL, Calhoun WJ, Choi AM. Low-dose carbon monoxide reduces airway hyperresponsiveness in mice. Am J Physiol Lung Cell Mol Physiol 2003;285:L1270-L1276.

23. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 1997;277:2002-2004.

24. Macdonald G, Kondor N, Yousefi V, Green A, Wong F, Aquino-Parsons C. Reduction of carboxyhaemoglobin levels in the venous blood of cigarette smokers following the administration of carbogen. Radiother Oncol 2004;73:367-371.

25. Lambrecht BN, Hoogsteden HC, Pauwels RA. Dendritic cells as regulators of the immune response to inhaled allergen: recent findings in animal models of asthma. Int Arch Allergy Immunol 2001;124:432^-446.

26. Meshi B, Vitalis TZ, Ionescu D, Elliott WM, Liu C, Wang XD, Hayashi S, Hogg JC. Emphysematous lung destruction by cigarette smoke: the effects of latent adenoviral infection on the lung inflammatory response. Am J Respir Cell Mol Biol 2002;26:52-57.

27. Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, Maestrelli P, Ciaccia A, Fabbri LM. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:822-826.

28. Laprise C, Laviolette M, Boulet M, Boulet LP. Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling. Eur Respir J 1999;14:63-73.

29. Foster PS, Yang M, Herbert C, Kumar RK. CD4(+) T-lymphocytes regulate airway remodeling and hyper-reactivity in a mouse model of chronic asthma. Lab Invest 2002;82:455-462.

30. De Bie JJ, Kneepkens M, Kraneveld AD, Jonker EH, Henricks PA, Nijkamp FP, van Oosterhout AJ. Absence of late airway response despite increased airway responsiveness and eosinophilia in a murine model of asthma. Exp Lung Res 2000;26:491-507.

31. Hamelmann E, Oshiba A, Paluh J, Bradley K, Loader J, Potter TA, Larsen GL, Gelfand EW. Requirement for CD8+ T cells in the development of airway hyperresponsiveness in a marine model of airway sensitization. J Exp Med 1996;183:1719-1729.

32. Stock P, Kallinich T, Akbari O, Quarcoo D, Gerhold K, Wahn U, Umetsu DT, Hamelmann E. CD8(+) T cells regulate immune responses in a murine model of allergen-induced sensitization and airway inflammation. Eur J Immunol 2004;34:1817-1827.

33. Kawasaki S, Takizawa H, Yoneyama H, Nakayama T, Fujisawa R, Izumizaki M, Imai T, Yoshie O, Homma I, Yamamoto K, et al. Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice. J Immunol 2001;166:2055-2062.

34. Schaniel C, Pardali E, Sallusto F, Speletas M, Ruedl C, Shimizu T, Seidl T, Andersson J, Melchers F, Rolink AG, et al. Activated murine B lymphocytes and dendritic cells produce a novel CC chemokine which acts selectively on activated T cells. J Exp Med 1998;188:451-463.

35. Wills-Karp M. IL- 12/IL-13 axis in allergic asthma. J Allergy Clin Immunol 2001:107:9-18.

36. Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR, Lo D. Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol 1999; 162:2477-2487.

37. MacLean JA, Ownbey R, Luster AD. T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophila. J Exp Med 1996; 184:1461-1469.

38. Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P. Targeted disruption of the chemokine eotaxin partially reduces antigeninduced tissue eosinophilia. J Exp Med 1997;185:785-790.

Katrien B. Moerloose, Romain A. Pauwels, and Guy F. Joos

Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium

(Received in original form September 7, 2004; accepted in final form April 10, 2005)

Supported by Ghent University, concerted action no. 1205698, and the Belgian Government, DWTC contract no. 12PS0299.

Correspondence and requests for reprints should be addressed to Katrien Moerloose, D.V.M., Department of Respiratory Diseases, Ghent University Hospital, Heymansinstituut 4de verdieping, De Pintelaan 185, Ghent B-9000, Belgium. E-mail:

This article has an online supplement, which is accessible from this issue's table of contents at

Am J Respir Crit Care Med Vol 172. pp 168-172, 2005

Originally Published in Press as DOI: 10.1164/rccm.200409-1174OC on April 14, 2005

Internet address:

Copyright American Thoracic Society Jul 15, 2005
Provided by ProQuest Information and Learning Company. All rights Reserved

Return to Carbachol
Home Contact Resources Exchange Links ebay