Glutathione depletion in rats impairs T-cell and macrophage immune function
M. K. Robinson, M. L. Rodrick, D. O. Jacobs, J. D. Rounds, K. H. Collins, I. B. Saporoschetz, J. A. Mannick and D. W. Wilmore
Laboratory for Surgical Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115.
Critical illness is associated with both immunosuppression and glutathione
deficiency. We determined if in vivo depletion of glutathione would
adversely affect immune status. Rats with normal glutathione levels and
those with glutathione stores depleted by diethyl maleate underwent
analysis of splenocyte function and mesenteric lymph node lymphocyte
function. Lymphocytes of the spleen and mesenteric lymph nodes were tested
for concanavalin A proliferative response and interleukin 2 production.
Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells
was also measured. Glutathione-depleted animals had significantly decreased
lymphocyte proliferation and decreased production of tumor necrosis factor
and interleukin 6 but unaltered interleukin 2 production. These findings
indicate that in vivo glutathione deficiency impairs macrophage and T-cell
function. Because glutathione depletion may occur in sepsis, trauma, and
shock, treatments that help maintain glutathione levels may enhance
immunocompetence and thus improve the ability of patients to recover from
critical illness.
