INCREASED LEVELS OF IFN-GAMMA IN THE TRIGEMINAL GANGLION CORRELATE WITH PROTECTION AGAINST HSV-1-INDUCED ENCEPHALITIS FOLLOWING SUBCUTANEOUS ADMINISTRATION WITH ANDROSTENEDIOL

Androstenediol (AED) is a metabolic product of dehydroepiandrosterone (DHEA), an adrenal steroid known to possess immunomodulatory character istics. The present study was undertaken to assess the efficacy of AED treatment in mice ocularly infected with herpes simplex virus type 1 (HSV-1). The subcutaneous administration of 320 mg/kg AED 4 h prior to viral inoculation was found to enhance the survival of HSV-1-infected mice while lower doses (32.0-100.0 mg/kg) were without effect. Howeve r, there were no apparent differences in the viral load in the eye or trigeminal ganglion (TG) 3 or 6 days post infection (p.i.) in vehicle- or AED (320 mg/kg)-treated mice. Likewise, there were no differences in the expression of cytokine or chemokine mRNAs in the eyes or TG ear ly (i.e., 3 days p.i.) following infection. However, by 6 days p.i., t here was a significant increase in the expression of the chemokines IP -10, MCP-1, and RANTES and the cytokines interleukin-6 (IL-6) and inte rferon-gamma (IFN-gamma) in the AED (320 mg/kg)-treated mice compared to vehicle-treated controls as determined by reverse transcription (RT )-polymerase chain reaction (PCR) and quantitative PCR (for IFN-gamma) . Likewise, there was a corresponding increase in IFN-gamma and IL-2 b ut not IL-12 protein in the TG of AED-treated mice 6 days p.i. AED-tre atment also induced a rise in splenic natural killer activity in a dos e- and time-dependent fashion. Collectively, these results suggest tha t the protective effect following subcutaneous administration of AED i s associated in a rise in selective type 1 cytokines (IL-2 and IFN-gam ma) as well as natural killer activity. (C) 1998 Elsevier Science B.V. All rights reserved.