Acetylcholine-esterase inhibitor pyridostigmine decreases T cell overactivation in patients infected by HIV.
HIV infection is characterized by persistent immune activation, increased production of proinflammatory cytokines, and rapid T cell turnover. The autonomic nervous system exerts a regulatory effect on the inflammatory response mediated by acetylcholine. We investigated whether an acetylcholine esterase inhibitor would diminish the T cell overactive phenotype characteristic of chronically infected HIV patients. We carried out a proof-of-concept, placebo-controlled study involving 19 subjects chronically infected with HIV-1. Nine patient received pyridostigmine and 10 took a placebo. T cell activation measured by expression of CD69 (p = 0.025) diminished in those taking pyridostigmine. The drug also diminished in vitro T cell proliferation induced by PMA and ionomycin (p = 0.026). IFN-gamma release was diminished in the pyridostigmine group (p = 0.016) and expression of IL-4 (p = 0.010) and IL-10 (p = 0.015) increased. Here we showed that pyridostigmine is able to modify T cell overactivation and proliferation in patients chronically infected with HIV. Pyridostigmine led to an increase in the antiinflammatory cytokine IL-10 and a decrease in T cell proliferation and production of the proinflammatory cytokine IFN-gamma.
Valdés-Ferrer
Sergio Iván
SI
Department of Neurology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Universidad Nacional Autónoma de México , Mexico City DF, Mexico 14000. svaldesfer@nshs.edu
Crispín
José C
JC
Belaunzarán
Pablo Francisco
PF
Cantú-Brito
Carlos G
CG
Sierra-Madero
Juan
J
Alcocer-Varela
Jorge
J
D000328:Adult; D049109:Cell Proliferation; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011729:Pyridostigmine Bromide / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D002800:Cholinesterase Inhibitors; D016753:Interleukin-10; D007371:Interferon-gamma; D011729:Pyridostigmine Bromide