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INFLAMMATION AND IMMUNOPHARMACOLOGY

Mechanisms Involved in the Enhancement of Allergic Airways Neutrophil Influx by Permanent C-Fiber Degeneration in Rats

Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil (C.F.F.-P., I.A.D.S., E.A.C., G.D.N., E.A.); and Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil (S.A.T., M.N.M.)

This study was undertaken to clarify the mechanisms by which C-fiber degeneration at neonatal stages exacerbates the inflammatory responses of rat airways. Rats were treated with capsaicin at neonatal stages and immunized with ovalbumin (OVA) at adult ages. Challenge of capsaicin-pretreated rats with OVA promoted a higher influx of neutrophils in bronchoalveolar lavage (BAL) fluid compared with the vehicle group. No significant differences were found for the other cell types. The increased adhesion of N-formyl-methionyl-leucyl-phenylalanine (fMLP; 0.1 µM)- and phorbol myristate acetate (PMA; 1 µM)-treated neutrophils to fibronectin-coated wells did not differ among vehicle- and capsaicin-pretreated rats. Additionally, fMLP (10 µM), platelet-activating factor (0.1 µM), and substance P (50 µM) induced a significant neutrophil chemotaxis, but no differences were found among vehicle and capsaicin groups. Increased levels of tumor necrosis factor (TNF)-, interleukin (IL)-6, IL-10, and leukotriene B₄ in BAL fluid as well as higher expression of cytokine-induced neutrophil chemoattractant (CINC)-3 in lung homogenates were detected in the capsaicin group compared with vehicle group. In the capsaicin group, chronic treatment with compound 48/80 restored the TNF- levels to control values and prevented the neutrophil influx in BAL fluid. The enhanced production of TNF-, superoxide anion, and nitrite by isolated alveolar macrophages in response to lipopolysaccharide (3 µg/ml), PMA (10 nM), and/or zymosan (100 particles/cell) did not differ between vehicle- and capsaicin-pretreated rats. In conclusion, chronic neuropeptide depletion promoted by neonatal capsaicin treatment up-regulates airways mast cells, which upon activation by antigen at adult ages, release large amounts of cytokines such as TNF- and CINC-3 that accounts for the massive airways neutrophil infiltration.

Address correspondence to: Dr. Edson Antunes, Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, P.O. Box 6111, CEP 13084-971, Campinas, SP, Brazil. E-mail: edson.antunes{at}uol.com.br

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