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

SUMMARY 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 of 51 Cr‐labelled rat blood PMNL and 111 In‐labelled T lymphocytes to the joints of rats with adjuvant arthritis was measured along with plasma protein extravasation, which was quantified using 125 I‐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.