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 characteristics. 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. However, 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 early (i.e., 3 days p.i.) following infection. However, by 6 days p.i., there was a significant increase in the expression of the chemokines IP-10, MCP-1, and RANTES and the cytokines interleukin-6 (IL-6) and interferon-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 but not IL-12 protein in the TG of AED-treated mice 6 days p.i. AED-treatment also induced a rise in splenic natural killer activity in a dose- and time-dependent fashion. Collectively, these results suggest that the protective effect following subcutaneous administration of AED is associated in a rise in selective type 1 cytokines (IL-2 and IFN-gamma) as well as natural killer activity.
Carr
D J
DJ
Department of Microbiology, Immunology, and Parasitology, LSU Medical Center, New Orleans, LA 70112-1393, USA. dcarr@lsumc.edu
D045930:Anabolic Agents / Q000494:pharmacology*; D015114:Androstenediol / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood; D018792:Encephalitis, Viral / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D018259:Herpesvirus 1, Human / Q000276:immunology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000032:analysis / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D016019:Survival Analysis; D012668:Trigeminal Ganglion / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D019562:Viral Load
D045930:Anabolic Agents; D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D018664:Interleukin-12; D007371:Interferon-gamma; D015114:Androstenediol; D003345:Corticosterone