Severe inflammatory arthritis and lymphadenopathy in the absence of TNF

Abstract

It has been postulated that TNF has a pivotal role in a cytokine cascade that results in joint inflammation and destruction in rheumatoid arthritis (RA). To evaluate this, we examined the response of TNF-deficient (Tnf-/-) mice in two models of RA. Collagen-induced arthritis (CIA) was induced by injection of chick type II collagen (CII) in CFA. Tnf-/- mice had some reduction in the clinical parameters of CIA and, on histology, significantly more normal joints. However, severe disease was evident in 54% of arthritic Tnf-/- joints. Tnf-/- mice had impaired Ig class switching, but preserved T cell proliferative responses to CII and enhanced IFN-γ production. Interestingly, CII-immunized Tnf-/- ..