The role of T(H)1 and T(H)2 cytokines in HSV-1-induced corneal scarring

• Published in: Ocular immunology and inflammation Vol. 10; no. 2; pp. 105 - 116
• Main Authors: Osorio, Yanira, Sharifi, Behrooz G, Perng, Guey, Ghiasi, Neema S, Ghiasi, Homayon
• Format: Journal Article
• Language: English
• Published: England 01.06.2002
• Subjects: Animals; Cornea - pathology; Cornea - virology; Cytokines - physiology; Defective Viruses; Female; Herpesvirus 1, Human - pathogenicity; Keratitis, Herpetic - pathology; Keratitis, Herpetic - prevention & control; Keratitis, Herpetic - virology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Th1 Cells - immunology; Th2 Cells - immunology; Virulence
• ISSN: 0927-3948; 1744-5078
• DOI: 10.1076/ocii.10.2.105.13982

To determine the relative impact of T(H)1 and T(H)2 cytokines on the induction of corneal scarring. BALB/c and C57BL/6 mice were infected ocularly with herpes simplex virus type 1 (HSV-1)-recombinant viruses expressing either IL-2, IL-4, IFN-gamma, IL-12p35, or IL-12p40. Parental virus and recombinant viruses in one group (dLAT2903, HSV-IL-2, HSV-IL-4, and HSV-IFN-gamma) contained an intact neurovirulence gene, gamma34.5, while the second set of recombinant viruses (DM33, dbl-IL2, dbl-IL4, dbl-IFNgamma, dbl-IL12p35, and dbl-IL12p40) lacked the gamma34.5 gene. In the presence of gamma34.5, viruses that expressed either IL-2 or IL-4 reduced the severity of corneal scarring in both BALB/c and C57BL/6 mice compared with the parental virus. In contrast, the recombinant virus expressing IFN-gamma was not protective in BALB/c mice, while it exacerbated corneal scarring in C57BL/6 mice compared with the parental or wt McKrae virus. In the absence of the gamma34.5 gene, recombinant viruses expressing IL-2, IL-4, IFN-gamma, IL-12p35, or IL-12p40 did not induce any corneal scarring. Our results suggest the following: (1). IL-2 and IL-4 are both involved in protection against HSV-1-induced corneal scarring; (2). IFN-gamma is not involved in protection against HSV-1-induced corneal scarring; and (3). the degree of neurovirulence plays a major role in the protection against or induction of corneal scarring.