Oxidoreductase macrophage migration inhibitory factor is simultaneously increased in leukocyte subsets of patients with severe sepsis

Abstract

The oxidoreductase Macrophage Migration Inhibitory Factor (MIF) is discussed as a promising target for immunomodulatory therapy in patients with severe sepsis. Moreover, MIF expresses tautomerase as well as thiol-protein oxidoreductase activities and has a potential role in cellular redox homeostasis, apoptosis inhibition, endotoxin responsiveness as well as regulation of nuclear transcription factors. To further elucidate a potential role of intracellular MIF in severe sepsis, we assessed alterations of intracellular MIF content in peripheral blood leukocytes of patients with severe sepsis in comparison to healthy controls and non-septic patients after major surgery. Intracellular MIF was significantly elevated simultaneously in lymphocytes, B-cells, macrophages and granulocytes of patients with severe sepsis when compared to healthy control individuals (p < 0.05) and increased when compared to non-septic patients after major surgery. In parallel, plasma MIF levels were elevated in severe sepsis (p < 0.05). There was no difference of intracellular MIF in lymphocytes, B-cells, macrophages or granulocytes between surviving and non-surviving patients with severe sepsis (p > 0.05). However, in survivors LPS ex vivo stimulation increased MIF secretion but not in non-survivors of sepsis (p < 0.05). This finding underlines the role of intracellular MIF in inflammatory diseases. It suggests monitoring of intracellular MIF in further clinical and non-clinical research valuable.

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

“…Indeed, estradiol, progesterone, and glucocorticoids are expressed at particularly high levels during the neonatal period; have a short half-life; and stimulate MIF production by immune cells in vitro and in vivo (27,47,48). Because newborn whole blood and monocytes show somewhat different MIF secretion profiles in response to E. coli and GBS, T cells, B cells, neutrophils, eosinophils, and platelets may participate to release MIF in response to microbial stimulation (49)(50)(51)(52). Although the main source of circulating MIF is still unknown, our data indicate that production of MIF by newborn monocytes may play an important role in the control of inflammatory responses, as MIF acts in an autocrine fashion to stimulate the production of inflammatory cytokines by newborn monocytes.…”

Macrophage migration inhibitory factor (MIF): A promising biomarker

“…Among pro-inflammatory cytokines, MIF is distinguished by being present in many cell types in pre-formed, intracytoplasmic pools [9]. Using flow cytometry analysis, MIF was found to be elevated simultaneously in lymphocytes, B-cells, macrophages and granulocytes in patients with severe sepsis when compared to healthy control individuals [31]. …”

Distinct patterns of serum and urine macrophage migration inhibitory factor kinetics predict death in sepsis: a prospective, observational clinical study

“…Considering that we did not always detect statistically significant difference between the outcome groups when only single measurements were compared, the novel finding about the distinct kinetics indicates that repeated serum MIF level measurements in the same patient can be better predictors of the outcome than single time-point measurement at the ICU. Indeed, the significant prognostic value of MIF was not found in some previous studies, in which the authors performed only one measurement of its serum level [45][46][47] . The increasing levels of serum MIF associated with the fatal outcome can be assumed to be related to the progression of the disease.…”

“…The gradually increasing serum MIF level may serve as a marker for the excessively intensifying proinflammatory activity, which can be an early warning sign for healthcare personnel to initiate more aggressive treatments before fatal consequences develop. It should be noted also that MIF is present in different cell types in pre-formed, intracytoplasmic pools [47][48][49][50][51][52] , thus its increasing levels may also reflect escalating tissue damage and necrosis. Interestingly, in survivor and deceased females the patterns of serum MIF kinetics were somewhat different from males.…”