Friedman H, Klein T, Specter S, Pross S, Newton C, Blanchard D K, Widen R
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612.
Adv Biochem Psychopharmacol. 1988;44:125-37.
It is widely recognized that various microorganisms including viruses have immunomodulatory effects and, under appropriate circumstances, may markedly suppress the immune response mechanisms. Cannabinoids present in marijuana also have immunomodulatory effects. In the present studies THC as well as its metabolic product 11-OH THC were studied in regard to their effects in vivo and in vitro on selected parameters of the immune response system known to be important in antiviral resistance, including immunity to retroviruses. Cannabinoids markedly suppressed the ability of murine macrophages to spread on glass (an important functional marker of macrophages) as well as to phagocytize yeast particles. Splenic macrophage cultures treated with the cannabinoids also were deficient in their ability to produce interleukin 1 on appropriate stimulation with bacterial LPS. Spleen cells capable of producing antibody to sheep erythrocytes when stimulated with this antigen in vitro were markedly affected when treated with graded doses of THC or 11-OH THC. Furthermore, the blastogenic responsiveness of normal mouse splenocytes to the T-cell mitogens Con A and PHA as well as the B-cell mitogen E. coli LPS was markedly suppressed by graded concentrations of the cannabinoids in doses that did not affect the viability of the cells. Natural killer cell activity of normal mouse spleen cells was also markedly inhibited by THC and 11-OH THC. Similarly, these cannabinoids suppressed the blastogenic responsiveness and NK activity of human peripheral blood leukocytes from normal individuals. The ability of mouse spleen cells to produce interferon on in vitro stimulation was also suppressed by THC. In addition, injection of THC into mice suppressed blastogenic responsiveness of spleen cells, NK activity, and the production of interferon by lymphoid cells. Thus, it was apparent that these cannabinoids had immunomodulatory effects, both in vivo and in vitro, at noncytotoxic small doses and impaired the ability of the lymphoid cells to express immune function necessary for antiviral resistance.
人们普遍认识到，包括病毒在内的各种微生物具有免疫调节作用，在适当情况下，可能会显著抑制免疫反应机制。大麻中含有的大麻素也具有免疫调节作用。在本研究中，对四氢大麻酚（THC）及其代谢产物11-羟基四氢大麻酚（11-OH THC）在体内和体外对免疫反应系统的选定参数的影响进行了研究，这些参数已知在抗病毒抗性中很重要，包括对逆转录病毒的免疫力。大麻素显著抑制小鼠巨噬细胞在玻璃上的铺展能力（巨噬细胞的一个重要功能标志物）以及吞噬酵母颗粒的能力。用大麻素处理的脾巨噬细胞培养物在受到细菌脂多糖适当刺激时产生白细胞介素1的能力也存在缺陷。当用分级剂量的THC或11-OH THC处理时，在体外受到该抗原刺激时能够产生抗绵羊红细胞抗体的脾细胞受到显著影响。此外，正常小鼠脾细胞对T细胞有丝分裂原刀豆蛋白A（Con A）和植物血凝素（PHA）以及B细胞有丝分裂原大肠杆菌脂多糖（E. coli LPS）的增殖反应性被分级浓度的大麻素显著抑制，而这些剂量并不影响细胞的活力。正常小鼠脾细胞的自然杀伤细胞活性也被THC和11-OH THC显著抑制。同样，这些大麻素抑制了正常个体人外周血白细胞的增殖反应性和自然杀伤细胞活性。THC还抑制了小鼠脾细胞在体外刺激时产生干扰素的能力。此外，向小鼠注射THC会抑制脾细胞的增殖反应性、自然杀伤细胞活性以及淋巴细胞产生干扰素的能力。因此，很明显这些大麻素在体内和体外均在无细胞毒性的小剂量下具有免疫调节作用，并损害了淋巴细胞表达抗病毒抗性所需免疫功能的能力。
