Studies of skin-window exudate human neutrophils: increased resistance to pentoxifylline of the respiratory burst in primed cells.

Human neutrophils were isolated both from peripheral blood (PB) and from aseptic inflammatory exudates obtained by the Senn's skin window technique (SW). The respiratory burst (O2- production) induced by in response to n-formyl-methionyl-lencyl-phenylalanine (fMLP) and by serum-treated zymosan (STZ) was investigated using a microplate assay. SW neutrophils were primed to enhanced fMLP-dependent O2- production in response to fMLP but not to STZ. Pentoxifylline, a cAMP-elevating drug, dose-dependently inhibited the respiratory burst in any experimental condition, but the dose-effect curves were markedly different according the stimulant used and the source of the cells. With fMLP as stimulant, a significant inhibition of the O2- production by PB neutrophils was obtained using doses of 10 micrograms/ml, while SW neutrophils were inhibited only by doses equal or higher than 100 micrograms/ml. With STZ as stimulant, the inhibition of the respiratory burst of PB neutrophils and of SW neutrophils was obtained only with doses higher than 400 micrograms/ml and 1 mg/ml respectively. Pentoxifylline dose-dependently (10 micrograms/ml to 1 mg/ml) increased the intracellular adenosine 3'-5'-cyclic monophosphate (cAMP) to the same extent in SW and in PB neutrophils. These data indicate that the priming of neutrophil oxidative metabolism by in vivo inflammation is associated with an increase in the resistance to the regulating effect of cAMP on the fMLP-dependent activation pathway of NADPH oxidase. The fact that therapeutic doses of pentoxifylline do not inhibit the respiratory burst of primed neutrophils may have relevance in the interpretation of the clinical effects of this drug.

T-cell-mediated epineurial vasculitis and humoral-mediated microangiopathy in cryoglobulinemic neuropathy.

We used immunohistochemistry to assess the role of humoral and cellular factors in endoneurial microangiopathy and epineurial vasculitis in 15 nerve biopsies of patients with axonal neuropathy and monoclonal or mixed cryoglobulinemia (CG). Deposition of immunoglobulins and cytolytic complement was detected in endoneurial capillaries of patients with mixed CG. Epineurial inflammatory infiltrates containing beta2-integrin-positive lymphocytes and monocytes surrounded arterioles expressing cell adhesion molecules, thus suggesting a cell-mediated pathogenesis of the epineurial vasculitis. On the other hand, the absence of immune complex deposition and polymorphonuclear elements suggests a minor role for the humoral mechanisms in the formation of the vasculitic lesions. This study indicates that both cell-mediated mechanisms and immune complexes/cryoglobulins are involved, although at different levels, in the pathogenesis of CG neuropathy.

Increased serum levels of ICAM-1, ELAM-1 and TNF-alpha in inflammatory disorders of the peripheral nervous system.

Endothelial intercellular adhesion molecule-1 (ICAM-1) and glycoprotein E-selectin (ELAM-1) allow the homing of leukocytes to inflammation sites. A circulating form of ICAM-1 markedly increases in inflammatory CNS disorders. In the present study, the serum levels of ICAM-1, ELAM-1 and tumor necrosis factor-alpha (TNF-alpha) were measured in patients with acute (AIDP) and chronic (CIDP) inflammatory demyelinating polyneuropathies and cryoglobulinemic neuropathy (CGN). Immunoenzymometric assays revealed increased sICAM-1 levels in some of these patients; furthermore, high titres of ELAM-1 and TNF-alpha were detected in two patients with AIDP and one patient with CGN. Our data extend previous observations on inflammatory PNS disorders by showing that, in addition to ICAM-1, ELAM-1 also represents a useful marker of endothelial activation and that, taken together, the two molecules may serve as an indicator of specific pathogenetic mechanisms.

Monitoring of elastase in plasma of burned patients in relation to other inflammation parameters.

Twenty burned patients divided in three groups according to the severity of the lesions were investigated at 1- or 2-day intervals for up to 5 weeks after injury. Plasma elastase levels were elevated during the first day after injury and were correlated with the area of the burns. However, plasma elastase was rapidly bound and inactivated by protease inhibitors. Leucocyte counts, fever and the concentration of alpha-1-proteinase inhibitor were not correlated with the extent of the burn. The rise of plasma elastase was not accompanied by consumption of the elastase inhibitory capacity (EIC) of plasma, which increased to a plateau around day 5. The EIC values were in accord with the rise of alpha-1-proteinase inhibitor, the major anti-elastase agent in plasma. Studies of blister fluid in eight patients showed that the elastase content was higher than that of corresponding plasma, while the concentration of alpha 1-proteinase inhibitor and the EIC were comparable with those of plasma. Measurements of the levels of tumour necrosis factor released by stimulated macrophages in five patients with major burns showed no significant increase compared with controls.