IL-12 exacerbates helminth-mediated corneal pathology by augmenting inflammatory cell recruitment and chemokine expression.
Corneal inflammation (keratitis) is a major cause of visual impairment in Onchocerca volvulus infection. Previous studies showed that onchocercal keratitis can be induced in mice following s.c. immunization and intracorneal injection with soluble O. volvulus Ags (OvAg), and that the inflammatory response is dependent on T cells and IL-4. Since recombinant IL-12 impairs IL-4-dependent, Th2-mediated responses in other parasitic infections and in models of allergic asthma, the present study was undertaken to determine the effect of IL-12 on onchocercal keratitis. Mice were injected i.p. with IL-12 or saline at the time of initial sensitization to OvAg. Surprisingly, IL-12 treatment caused significant exacerbation of corneal pathology, which was associated with increased eosinophil and mononuclear cell infiltration into the corneal stroma. Consistent with the well-documented effect of IL-12 on Th1 cell development, corneas of IL-12-treated animals had elevated expression of the Th1 cytokine IFN-gamma and diminished expression of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13. However, corneas from these animals also had marked elevation of alpha- and beta-chemokines known to be active on eosinophils and mononuclear cells, including IFN-gamma-inducible protein (IP)-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, JE/monocyte chemotactic protein-1, RANTES (regulated upon activation, normal T expressed and secreted), and eotaxin. Together, these data indicate that IL-12 exacerbates OvAg-mediated corneal pathology by enhancing chemokine expression and recruitment of inflammatory cells.
Pearlman
E
E
Department of of Medicine, Case Western Reserve University, Cleveland, OH 44106-4983, USA.
Lass
J H
JH
Bardenstein
D S
DS
Diaconu
E
E
Hazlett
F E
FE
Albright
J
J
Higgins
A W
AW
Kazura
J W
JW
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D018925:Chemokines / Q000819:agonists* / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects; D018664:Interleukin-12 / Q000009:adverse effects*; D007634:Keratitis / Q000469:parasitology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects; D017181:Onchocerca volvulus / Q000276:immunology / Q000472:pathogenicity*; D009855:Onchocerciasis / Q000276:immunology / Q000473:pathology*
D000947:Antigens, Helminth; D018925:Chemokines; D018664:Interleukin-12