Medical Hypotheses (1988) 26, 229-230 0 Longman Group UK Ltd 1988

HIV Virus, Prostaglandins and. Essential Fatty Acids; a Suggested Mechanism for T Helper Cell Penetration

K. S. VADDADI* and U. N.’ DASt

+Depatiment of Psychiatry, Crawley Hospital, West Green Drive, Crawley, Sussex, RHI 7 7DH, U.K. tThe Nizam’s institute of Medical Sciences, Hyderabad, India (reprint requests to K. S. V.)

Abstract - Prostaglandins and or its precursors are present in certain body fluids. It has been suggested that critical concentrations of PGE are essential for the HIV to penetrate a lymphocyte. Certain clinical implications of this hypothesis have been discussed.

AIDS is a state of immunosuppression caused by the HIV retrovirus. The virus shows marked tropism for T helper cells, using the T4 cell surface antigen as a receptor. The affected cells lose their functional capacity. The mechanism and factors which enable the HIV virus to penetrate OK Tb+ cells are not well understood. If this mechanism were known, then it would throw open new avenues in the prevention and treatment of AIDS. We suggest that factors that may contribute to the invasion capacity of HIV are prostaglandins. The HIV virus is present in blood, saliva, tears, semen and breast milk, all of which contains prostaglandins (PGs) or precu- rosrs of PGs, namely essential fatty acids (1, 2, 3. 4, 5). Semen in particular has large quantities of prostaglandins in 20-25 ug/ml range to 60+-15 ug/ml range (6, 7). It is believed that the PGs in semen may be concerned with motility of the female genital tract, ensuring rapid transfer of sperm towards the ovum. Prolactin whose second messenger may be PGEr is found in high

concentrations in semen, and there is a positive correlation between prolactin concentrations and male fertility and sperm motility (8). Prolactin in tissues increases PG production (6). It is tempting to suggest that critical concentrations of prostaglandin E are needed for the HIV to penetrate a lymphocyte.

Recently a group of Japanese workers showed that PGE2 given via the anus to male rats produced a decrease in T-cell response to PHA in male rats but had no effect on female rats. It has been suggested that females are naturally more resistant to seminal immunosuppressants. Seminal PGE is absorbed through the rectum and may cause immunosuppression in male homosexuals making them more susceptible to viral infection. Recently indomethacin, a PG synthesis inhibitor, has been found to improve symptoms of AIDS patients (9). In vitro studies indomethacin increases lymphocyte mitogenic responses (10).

These effects are probably due to a cyclo-

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oxgenase mediated prostaglandin inhibition. These studies suggest involvement of prostaglan- dins in AIDS pathogenesis. In addition to the immunosuppressant effect of prostaglandins we also suggest the following mechanism: Critical concentrations of prostaglandin E may be needed for the HIV virus to facilitate its entry into a lymphocyte. This is supported by the observation that high PGE levels in some way enhance the capability of a sperm to penetrate an ovum in the fertilisation process (11). If this is true, it has important clinical implications. Lowering PGE levels in high risk groups using aspirin, alone or in combination with eicosapen- taenoic acid (marine fish oil). would lower PGE levels (12) and stop the ability of HIV to attack helper T cells and so prevent multiplication of the virus. This hypothesis of retrovirus penetr- ante of human helper T cells can easily be studied in in vitro studies using human lympho- cyte cultures in the presence or absence of pros- taglandin E blockers (aspirin. indomethacin, eicosapentaenoic acid). One woutd also need to study lymphocytes from males and females to see if continuous hormonal effects in females and high prolactin levels make lymphocytes from female subjects more resistant to a prostag- landin-facilitated mechanism of HIV virus penetrance.

MEDICAL HYPOTHESES

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