The role of T(H)1 and T(H)2 cytokines in HSV-1-induced corneal scarring.
OBJECTIVE
To determine the relative impact of T(H)1 and T(H)2 cytokines on the induction of corneal scarring.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Osorio
Yanira
Y
Department of Surgery, CSMC Burns & Allen Research Institute, Los Angeles, CA 90048, USA.
Sharifi
Behrooz G
BG
Perng
Guey
G
Ghiasi
Neema S
NS
Ghiasi
Homayon
H
D000818:Animals; D003315:Cornea / Q000473:pathology / Q000821:virology*; D016207:Cytokines / Q000502:physiology*; D003673:Defective Viruses; D005260:Female; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D016849:Keratitis, Herpetic / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014774:Virulence
D016207:Cytokines