Elevated
zinc serum concentrations have been shown to restore impaired immune response. Therefore, pharmacologic
zinc supplementation has been used to improve immune function, particularly in
intensive care patients. In these patients, Gramnegative
sepsis, the symptoms of which are predominantly caused by LPS-induced release of
monokines, represents a serious problem. We have recently shown that
zinc enhances induction of
TNF-alpha and
IL-1 beta in cultures of PBMC by LPS. By fluorescence polarization and infrared spectroscopic measurements we found that
zinc addition leads to decreased fluidity of the
hydrocarbon chains of LPS. Experiments at different temperatures showed that the less fluid gel (beta) phase of LPS is more effective in
cytokine induction than the more fluid liquid-crystalline (alpha) phase. Our studies suggest that the synergistic effect of
zinc on monokine induction by LPS is caused by direct interaction of
zinc with LPS altering the fluidity of the
hydrocarbon chains. Although this effect is
zinc specific, other divalent
ions, like
cobalt and
nickel, with a complex structure and size comparable to those of
zinc also enhance LPS-induced monokine secretion but to a much lesser extent. Our data indicate that the
zinc level represents a relevant clinical parameter in the treatment of Gram-negative
infection. This reveals potential risks in the therapeutic application of
zinc.