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 rabbit eye induces an inflammation of the retina characterized by hemorrhage, monocyte and neutrophil infiltration, and an increase in vascular permeability that peaks 24 h post-injection. Since the epiretinal vessels involved in this inflammation form part of the blood-retina barrier, we used this model to investigate the effects of the immunosuppressive cytokine TGF beta 1 on inflammation within the context of the central nervous system. We found that intra-vitreal injection of 1 microgram rh TGF beta administered concomitantly with rh IL-1 beta significantly reduced IL-1 beta-induced hemorrhage by 78%, and monocyte and neutrophil 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 increase 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 cellular inflammation accompanied this alteration in vascular permeability. These data indicate that whereas the local administration of TGF beta may be an effective inhibitor of cellular inflammation in the CNS, the effects on alterations in vascular permeability and accumulation of serum proteins may be more complex.
Cuff
C A
CA
Department of Epidemiology and Public Health, Yale University, New Haven, CT 06520, USA.
Martiney
J A
JA
Berman
J W
JW
Brosnan
C F
CF
D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D001813:Blood-Retinal Barrier; D002199:Capillary Permeability / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000633:toxicity; D007958:Leukocyte Count; D011817:Rabbits; D012166:Retinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology; D012173:Retinitis / Q000139:chemically induced* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000627:therapeutic use
D001798:Blood Proteins; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D016212:Transforming Growth Factor beta