Induction of suppurative arthritis in rabbits by Haemophilus endotoxin, tumor necrosis factor-α, and interleukin-1β

Because Haemophilus influenzae type b (Hib) is the principal cause of suppurative arthritis in young children and its lipooligosaccharide (LOS) is thought to be the main virulence factor, Hib endotoxin was evaluated for its ability to induce synovial inflammation in rabbits. Also, the role of the cytokines tumor necrosis factor-α (TNF α) and interleukin-1β (IL-1β) in mediating the synovial inflammatory process was studied. Intraarticular inoculation of 2 pg to 20 ng of Hib LOS produced a dose-dependent increase in concentrations of leukocytes and protein in synovial lavage fluid that was significantly modulated by concomitant administration of rabbit TNFα- and rabbit IL-1β-specific antibodies. Inoculation of joints with either 10⁴ IU of rabbit TNFα or 10 ng recombinant rabbit IL-1β induced synovial inflammatory changes similar to those observed after LOS intraarticular challenge. These data provide evidence for the role of Hib LOS in inducing suppurative arthritis and for the critical participation of TNFα and IL-1β in the initial events of the synovial inflammatory response.