L-tryptophan induced eosinophilia-myalgia syndrome.

We describe the spectrum of clinical and histologic abnormalities of 11 women with L-tryptophan induced eosinophilia-myalgia syndrome. The illness is characterized by musculoskeletal symptoms including myalgias, arthralgias and paresthesias. The physical findings consist of muscle tenderness, neuropathies, rash, peripheral and periorbital edema. Electroneurography performed in 10 patients demonstrated a neuropathy in 5 and myopathic changes in 3. Skin and muscle biopsies showed fascial edema, inflammation and perivascular infiltrates in the skin, whereas perineural infiltrates and venulitis were identified in muscle. Seven patients were treated with prednisone; eosinophilia disappeared promptly although myalgias and neuropathy persisted.

Generation of C5-derived peptides and other immune reactants in the sera of patients with systemic lupus erythematosus.

Activated complement components and immune complexes cause neutrophil aggregation in vitro and in vivo. We have previously demonstrated that sera of patients with active systemic lupus erythematosus (SLE) provoke the aggregation of normal neutrophils in vitro. In this study the serum or plasma of 4 such patients was fractionated on Sephadex G-75. In 3 patients neutrophil aggregating activity (NAA) was detectable in fractions which coeluted with reference C5-derived peptides (estimated molecular radius of 17,000). The activity of these fractions was inhibitable by antibodies to human C5. All patients also had activity that coeluted with reference immune complexes. In addition, material of apparent molecular radius under 12,000 that contributed to the neutrophil aggregating activity of SLE sera was detected. In separate experiments increased levels of C5a desarg were demonstrated during active disease by means of radioimmunoassay. These findings suggest that multiple neutrophil aggregants circulate during the course of active SLE. The formation of intravascular leukoaggregates may contribute to endothelial injury in this disease.

Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo.

Human blood neutrophils exposed to appropriate stimuli aggregate, degranulate and generate superoxide anion (O2-). These responses are anteceded by mobilization of membrane-associated calcium, monitored as a decrease in fluorescence of cells preloaded with chlortetracycline (CTC). We studied the effects, both in vitro and in vivo, of non-steroidal anti-inflammatory agents (aspirin, indomethacin, ibuprofen and piroxicam) on these neutrophil responses to three stimuli: a chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (FMLP); a tumor promotor, phorbol myristate acetate (PMA); and a lectin, concanavalin A (Con A). The effects of these drugs were compared with those of two polyenoic inhibitors of arachidonate metabolism: eicosatrienoic acid (ETI) and eicosatetraynoic acid (ETYA). The pattern of inhibition of neutrophil functions varied both with inhibitor and the nature of the stimulus. Thus, aspirin, piroxicam, ETYA and ETI inhibited neutrophil aggregation, degranulation, and O2- generation in response to FMLP, whereas ibuprofen inhibited only aggregation and degranulation and indomethacin only inhibited aggregation. None of the agents inhibited aggregation or degranulation induced by PMA or Con A: only piroxicam inhibited O2- generation in response to PMA or Con A. ETI and ibuprofen inhibited decrements of CTC fluorescence induced by FMLP, but whereas ETI inhibited the CTC response to PMA or Con A, ibuprofen was without effect. The agents had varying effects on binding of the stimulus [( 3H]FMLP, [3H]Con A), but these did not correlate with neutrophil responses to the ligands. Neutrophils from subjects taking therapeutic doses of ibuprofen, indomethacin, or piroxicam showed profiles of inhibited responses to FMLP similar to those observed with these agents in vitro. These data suggest that, although non-steroidal anti-inflammatory agents may inhibit discrete neutrophil functions both in vitro and in vivo, their effects do not duplicate those of polyenoic inhibitors of arachidonate metabolism. Moreover, since the susceptibility of neutrophils differed not only with respect to each inhibitor, but also to the stimulus, it is unlikely that all neutrophil responses are necessarily linked by a common pathway that is blocked by inhibitors of arachidonic acid metabolism.

Neutrophil aggregation induced by sera from patients with active systemic lupus erythematosus.

Activated complement components and immune complexes cause neutrophil (PMN) aggregation in vitro and in vivo, as in dialysis-induced neutropenia and adult respiratory distress syndrome. To investigate the possible role of PMN aggregation in systemic lupus erythematosus (SLE), we studied the capacity of 59 sera from 53 patients to induce aggregation of normal PMN in vitro. Neutrophil aggregating activity (NAA) was present in the sera of 26 of 28 patients with active SLE. The mean NAA in this group was significantly greater than that found in 13 patients with inactive SLE, 20 patients with rheumatoid arthritis, and 17 normal controls. In patients with SLE there was a positive correlation between disease severity and the quantitative measure of NAA. NAA did not correlate with serum C3 or C4 nor with the presence or absence of circulating immune complexes. High levels of NAA were particularly characteristic of central nervous system lupus. These data suggest that the formation of intravascular leukoaggregates may contribute to morbidity in SLE.