It has been postulated that TNF has a pivotal role in a cytokine cascade th
at results in joint inflammation and destruction in rheumatoid arthritis (R
A). To evaluate this, we examined the response of TNF-deficient (Tnf(-/-))
mice in two models of RA. Collagen-induced arthritis (CIA) was induced by i
njection of chick type II collagen (CII) in CFA. Tnf(-/-) mice had some red
uction in the clinical parameters of CIA and, on histology, significantly m
ore normal joints. However, severe disease was evident in 54% of arthritic
Tnf(-/-) joints. Tnf(-/-) mice had impaired Ig class switching, but preserv
ed T cell proliferative responses to CII and enhanced IFN-gamma production.
Interestingly, CII-immunized Tnf(-/-) mice developed lymphadenopathy and s
plenomegaly associated with increased memory CD4(+) T cells and activated l
ymph node B cells. Acute inflammatory arthritis was also reduced in Tnf(-/-
) mice, although again some mice exhibited severe disease. We conclude that
TNF is important but not essential for inflammatory arthritis; in each mod
el, severe arthritis could proceed even in the complete absence of TNF. The
se results call into doubt the concept that TNF is obligatory for chronic a
utoimmune and acute inflammatory arthritis and provide a rationale for furt
her studies into TNF-independent cytokine pathways in arthritis.