Immune suppression while awaiting surgery and following it: Dissociations between plasma cytokine levels, their induced production, and NK cell cytotoxicity

Surgery may render patients susceptible to life-threatening complications, including infections and later metastases. Suppression of cell mediated immunity (CMI) and perturbations in the cytokine network were implicated in these outcomes. The current study assessed the effects of various surgeries on a wide array of immune indices, and compared patients' pre-operative immune status to that of control subjects. A total of 81 subjects (controls, moderate and major surgeries) provided up to five daily blood samples. Whole blood procedures were conducted within hours of blood withdrawal, assessing NK cell number and cytotoxicity, and plasma cytokine levels and induced production (IFNγ, IL-6, IL-10, and IL-12). Our findings indicate that surgery reduced NK cell numbers/ml blood, and independently suppressed NK activity per NK cell and per ml blood. Among other perturbations in the cytokine network, pro-CMI cytokine production (IL-12 and IFNγ) was reduced by surgery. Surprisingly, plasma levels of IFNγ and IL-6 increased following surgery, while their in vitro induced production showed opposite effects. Patients awaiting surgery exhibited impaired IL-12 induced production and NK activity/ml, and reduced IFNγ plasma levels. No significant associations were found between NK cytotoxicity and Th1 cytokines, although these indices showed high correlations with other variables. Overall, our findings indicate that patients exhibit impaired immune functions even before operation, which seem to contribute to the evident post-operative immune suppression. In the peri-operative context, induced cytokine production and plasma cytokines levels reflect different processes. Last, we suggest that peri-operative suppression of NK activity is mediated by neuroendocrine responses rather than Th1 cytokines.