DIFFERENTIAL-EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1 ON INTERLEUKIN-1-INDUCED CELLULAR INFLAMMATION AND VASCULAR-PERMEABILITY IN THE RABBIT RETINA

Intra-vitreal injection of 300 U of interleukin (IL)-1 beta into the r abbit eye induces an inflammation of the retina characterized by hemor rhage, monocyte and neutrophil infiltration, and an increase in vascul ar permeability that peaks 24 h post-injection. Since the epiretinal v essels involved in this inflammation form part of the blood-retina bar rier, we used this model to investigate the effects of the immunosuppr essive cytokine TGF beta 1 on inflammation within the context of the c entral nervous system. We found that intra-vitreal injection of 1 mu g rh TGF beta administered concomitantly with rh IL-1 beta significantl y reduced IL-1 beta-induced hemorrhage by 78%, and monocyte and neutro phil infiltration by 53% and 62%, respectively. In contrast, TGF beta did not reduce the IL-1 beta-induced increase in vascular permeability . However, TGF beta by itself caused a statistically significant incre ase in serum proteins in perfused tissues of the eye, to give a 3.1 +/ - 0.4 fold increase in protein content over control values. No cellula r inflammation accompanied this alteration in vascular permeability. T hese data indicate that whereas the local administration of TGF beta m ay be an effective inhibitor of cellular inflammation in the CNS, the effects on alterations in vascular permeability and accumulation of se rum proteins may be more complex.