The Hpa Axis in HIV-1 Infection
Mahendra Kumar, Ph.D.,
University of Miami School of Medicine
Several lines of evidence suggest that neuroendocrine abnormalities in general and HPA activity in particular occur in both HIV-1 infection and individuals indulging in drug abuse. For instance, our studies showing attenuated norepinephrine as well as ACTH and cortisol responses to a cold pressor challenge in asymptomatic HIV-1+ individuals support such a concept (Kumar et al., 1991, 1993). Furthermore, these studies are congruent with the occurrence of autonomic neurophathies observed in HIV-1 infection (Freeman et al., 1990). Recently, we observed that the attenuated response to the cold pressor challenge was not a consequence of any possible reduction in pain perception in HIV-1 infection; furthermore, our data on investigations on mirror-star tracing and speech challenges also support that the neuroendocrine responses are compromised in HIV-1 infection. These findings could be related to studies showing that HIV-1 auxiliary protein, vpr, may interact with glucocorticoid receptors (Kino et al., 1999) and that a sequence of pre-gag region in HIV-1 genome has close homology with the sequence in the POMC-promoter region (Licinio et al., 1995), which is responsible for activating the POMC gene. Since HPA axis activity impacts cytokines such as IL-6, these findings are very important in understanding the pathogenesis in the central nervous system of HIV-1-infected individuals. This line of research has become all the more significant since recent studies show that highly potent antiretroviral therapies (HAART) may also induce metabolic disorders (Carr et al., 1998; Yanovski et al., 1999). This presentation will review the latest findings in this area and would also present research hypotheses needed to be tested for understanding the mechanisms involved in the development of neuroendocrine abnormalities in HIV-1-infected IDUs. (Supported by grants R01 MH 48637 and R01 DA12792)
- Carr A, Samaras K, Chisholm D, Cooper DA. Lancet 351:1881-3, 1998.
- Freeman R, Roberts MS, Friedman LS, Broadridge C. Neurology 40:575-80, 1990.
- Kino T, Gragerov A, Kopp JB, Stauber RH, Pavlakis GN, Chrousos GP. J Exptl Med 189:51-62, 1999.
- Kumar M, Morgan R, Szapocznik J, Eisdorfer C. J Acq Immune Def Syndromes 4:782-6, 1991.
- Kumar M, Kumar AM, Morgan R, Szapocznik J, Eisdorfer C. J Acq Immune Def Syndromes 6:61-5, 1983.
- Licinio J, Gold PW, Wong ML. Lancet 346:104-16, 1995.
- Yanovski JA, Miller KD, Kino T, Friedman TC, Chrousos GP, Tsigos C, Falloon J. J Clin Endocrn Metabol 84:1925-31, 1999.