The authors reported recently that endotoxaemia mediated elevated levels of tumour necrosis factor (TNF-alpha) and interleukin-1alpha (IL-1alpha) were involved in the pathophysiology of acute heat stroke patients. Pentoxifylline (PTX) is known to modulate neutrophil functions. In the present study the effects of PTX on lipopolysaccharide (LPS) and cytokine induced T-cell and macrophage (PhiM) activation, and on natural killer (NK) cell and lymphokine activated killer (LAK) cell mediated cytotoxicity were examined. Finally, the effect of PTX on the expression of adhesion molecules (LFA-1, Mac-1 and ICAM-1), and cytokine (IL-1alpha, IL-2, TNF-alpha, IL-6 and IFN-gamma) production and their surface receptor expression in response to LPS activation was investigated. PTX free cultures served as a control. Results revealed that PTX can down-regulate all the above-mentioned immunological parameters in a dosedependent manner. These findings might have far reaching clinical implications.

Incubation of human neutrophils with human immunoglobulin (Ig) E caused dose-dependent inhibition of adhesion, phagocytosis, secretion of myeloperoxidase, and oxygen radical production. The concentrations of IgE that caused 50% inhibition of adhesion, phagocytosis, and secretion were 2 +/- 0.3, 2.16 +/- 0.21, and 1.95 +/- 0.28 ng/ml, respectively. Oxidase activation as measured by luminol-dependent chemiluminescence by the receptor-mediated N-formyl-methionyl-leucyl-phenylalanine, phorbol 12-myristate 13-acetate, or the particulate stimulus Staphylococcus aureus was inhibited by IgE with concentrations causing 50% effect of 1.2 +/- 0.13, 1.09 +/- 0.16, and 0.6 +/- 0.09 ng/ml, respectively. IgE also inhibited oxygen consumption rate and cytochrome c reduction with similar K0.5 values. The effect of IgE was unlikely to be due to nonspecific cytotoxicity because trypan blue exclusion test and the cytoplasmic marker lactate dehydrogenase revealed that the cells retained their viability after IgE treatment. Similar or higher concentrations of IgG invoked either no inhibition or a slight enhancement of neutrophil functions. Pretreatment of neutrophils with IgG failed to affect the IgE-induced inhibition. Because the effect of IgE occurs at concentrations less than those reported in hyperimmunoglobulinemia E, we propose that direct inhibition of neutrophil functions may underlie the pathogenesis of recurrent infection associated with hyperimmunoglobulinemia E.

We fractionated the whole human seminal plasma on DEAE Sephadex A-50 ion exchange columns. Complete separation was achieved in seven peaks using different salt concentrations in phosphate buffer pH 6. The seminal plasma proteins were separated by sodium dodecyl-sulphate polyacrylamide gel electrophoresis. Human seminal plasma (SP) and its fractions were used in mixed lymphocyte reaction in vitro. Fractions 3, 4, and 7 were found to suppress the proliferation of human peripheral blood mononuclear cells to phytohemagglutinin and pokweed mitogen at a concentration of 10 micrograms ml-1 while stimulatory effect was observed at lower concentrations (1 microgram and 2.5 micrograms ml-1). Whole human SP and other fractions failed to suppress the proliferation of lymphocytes in vitro. Furthermore, the effect of human SP and its fractions was also investigated on phagocytic function of polymorphonuclear leukocytes (PMNs) using luminol dependent chemiluminescence assay stimulated with phorbol myristate acetate and opsonized yeast. Fractionated SP was found to have a suppressive effect on the luminol-dependent chemiluminescence of PMNs in the whole blood.

To determine whether endotoxemia and release of tumor necrosis factor (TNF-alpha) and/or interleukin 1 alpha (IL-1 alpha) are involved in the pathogenesis of heatstroke, 17 adult patients with a mean rectal temperature of 42.1 +/- 0.2 degrees C were studied. Blood samples were taken on admission and after cooling was completed. TNF-alpha and IL-1 alpha levels were measured by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) content was measured by the chromogenic substrate modification of the Limulus amebocyte lysate. TNF-alpha, IL-1 alpha, and LPS were elevated in all patients [199 +/- 25 (SE) pg/ml, 480.5 +/- 68.3 pg/ml, and 8.60 +/- 1.19 ng/ml, respectively, compared with normal control values of 31.4 +/- 8.4 pg/ml, 53.7 +/- 5.32 pg/ml, and less than 9 pg/ml]. There was no significant correlation between temperature and the circulating concentration of TNF-alpha, IL-1 alpha, and LPS. Postcooling TNF-alpha, IL-1 alpha, and LPS concentrations were significantly decreased but still above normal control values. The findings suggest that these mediators may have a role in the pathogenesis of heatstroke that could change the strategy of management.