Modulation of allergic inflammation in mice deficient in TNF receptors

Tumor necrosis factor-alpha (TNF) is implicated as an important proinflamma tory cytokine in asthma. We evaluated mice deficient in TNF receptor 1 (TNF R1) and TNFR2 [TNFR(-/-) mice] in a murine model of allergic inflammation a nd found that TNFR(-/-) mice had comparable or accentuated responses compar ed with wild-type [TNFR(+/+)] mice. The responses were consistent among mul tiple end points. Airway responsiveness after methacholine challenge and br onchoalveolar lavage (BAL) fluid leukocyte and eosinophil numbers in TNFR(- /-) mice were equivalent or greater than those observed in TNFR(+/+) mice. Likewise, serum and BAL fluid IgE; lung interleukin (IL)-2, IL-4, and IL-5 levels; and lung histological lesion scores were comparable or greater in T NFR(-/-) mice compared with those in TNFR(+/+) mice. TNFR(+/+) mice chronic ally treated with anti-murine TNF antibody had BAL fluid leukocyte numbers and lung lesion scores comparable to control antibody-treated mice. These r esults suggest that, by itself, TNF does not have a critical proinflammator y role in the development of allergic inflammation in this mouse model and that the production of other cytokines associated with allergic disease may compensate for the loss of TNF bioactivity in the TNFR(-/-) mouse.