The role of tumour necrosis factor-alpha and IL-1 in polymorphonuclear leucocyte and T lymphocyte recruitment to joint inflammation in adjuvant arthritis

Abstract

The mediators involved in leucocyte recruitment to joints during arthritis are not fully defined, but two important proinflammatory cytokines, IL-1 and tumour necrosis factor-alpha (TNF-α), are produced in joints in rheumatoid arthritis (RA). We investigated in the rat adjuvant arthritis model whether endogenous IL-1 and TNF-α contribute to joint inflammation and polymorphonuclear leucocyte (PMNL) and T lymphocyte infiltration. The migration of⁵¹ Cr-labelled rat blood PMNL and ¹¹¹In-labelled T lymphocytes to the joints of rats with adjuvant arthritis was measured along with plasma protein extravasation, which was quantified using ¹²⁵I-labelled human albumin. Rats with active arthritis of 5 days' duration received i.p. non-immune serum, polyclonal neutralizing anti-serum to rat TNF-α, antiserum to IL-α and IL-β or both anti-TNF plus anti-IL-l for 5 days. Treatment with anti-IL-1α and IL-1β did not affect plasma protein extravasation, or PMNL or T lymphocyte accumulation in the joints (i.e. talar joint, hind paws, and tail) despite the fact that this treatment inhibited 80–90% of the PMNL migration into dermal sites injected with IL-1α or IL-1β In contrast, anti-TNF-β treatment significantly improved clinical scores, decreased plasma protein extravasation by 60–80%, inhibited PMNL accumulation by 40–50% and decreased T lymphocyte accumulation by 30–50%. Treatment with anti-IL-1, together with anti-TNF-α, significantly potentiated the inhibition of T lymphocyte accumulation observed with anti-TNF-α alone. These results indicate that endogenous TNF-α production may play an important role in the inflammatory changes and leucocyte recruitment in this experimental model of human arthritis, while IL-1 may have a less important role in leucocyte recruitment to these joints.