IL-17 as a potential target for modulating airway neutrophilia.
Several chronic inflammatory airway diseases are characterized by an increased number of neutrophils in the airways. There is evidence that the recruitment of these neutrophils can be controlled by certain T-lymphocytes. However, the mechanisms behind this T-cell control of airway neutrophilia are poorly understood. In this review, we summarize the evidence that interleukin (IL)-17 released from T-lymphocytes of the CD45RO+ subset can link the activation of these T-cells to the recruitment and activation of neutrophils. This evidence suggests that pharmacotherapeutical modulation of neutrophilic airway inflammation can be achieved using several different strategies, including inhibition of IL-17 production by cAMP elevating agents or certain nuclear factor inhibitors, neutralization of released IL-17 protein by specific anti-IL-17-antibodies, blockade of the IL-17 receptor as well as inhibition of certain MAP kinases mediating the post receptor effects of IL-17 in airway cells. Additional studies on animals in vivo and patients, respectively, are needed to further evaluate the pharmacotherapeutical potential of these strategies.
Laan
Martti
M
Lung Pharmacology Group, Department of Respiratory Medicine Allergology, Guldhedsgatan 10A, Gothenburg, SE-413 46, Sweden. martti.laan@hjl.gu.se
Lindén
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008775:Methylprednisolone / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012140:Respiratory Tract Diseases / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; C109985:IL17RA protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D016572:Cyclosporine; D008775:Methylprednisolone