Interleukin-1 enhances the development of type II collagen-induced arthritis only in susceptible and not in resistant mice

The development of type II collagen-induced arthritis (CIA) in DBA/1 mice is readily accelerated by treatments with interleukin-1β (IL-1β). In an attempt to further characterize this IL-1β-mediated enhancement of CIA, we first examined the effects of IL-1β treatments in other “CIA-susceptible” strains and “CIA-resitant” mice. It was observed that treatments with IL-1β also enhanced the onset of arthritis in two B10 recombinant CIA-susceptible strains, B10.T (6R) and B10.DA, and in the SJL mice which develop CIA with a relatively low and variable incidence. On the other hand, IL-1β failed to augment the expression of arthritic disease in several CIA-resistant strains. We also investigated the potentiating effects of IL-1β in mice that were depleted of L3T4 + T cells. It was found that the ability of IL-1β to accelerate the development of CIA was significantly reduced in DBA/1 mice pretreated with the monoclonal anti-L3T4 antibody. In further studies, we demonstrated that the induction of CIA upon transfer with collagen-primed spleen cells was also augmented by IL-1β, and this enhancing effect by IL-1β on the adoptive transfer of CIA was associated with a significant increase in the levels of serum anti-collagen antibodies. Moreover, IL-1β treatments did not potentiate the induction of CIA in mice that were transferred with either collagen-immune splenic cells that were depleted of L3T4 + T cells or only T cells obtained from collagen-immunized animals. However, IL-1β enhanced the development of arthritis in animals that had been transferred with two subpopulations of collagen-immune cells: (i) enriched T cells and (ii) splenic cells that were depleted of L3T4 + T cells. Thus, IL-1β potentialed the inflammatory responses in animals that were genetically predisposed to developing arthritis. In contrast, IL-1β was incapable of accelerating the development of arthritis in various mouse strains that were genetically resistant to CIA. The administration of IL-1β also failed to potentiate the development of CIA in L3T4-deficient mice or in animals transferred with collagen-primed spleen cells that were depleted of L3T4 + T cells. These results indicate that IL-1β readily accelerates the induction of arthritis when the disease is present, but that IL-1β is incapable of promoting the expression of the arthritis in the absence of underlying disease.