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Roxithromycin (RU 28965) a new semisynthetic macrolide has been reported to display an antibacterial spectrum and activity in vitro similar to those of others macrolides. However, roxithromycin seems more efficient than erythromycin in in vivo experimental infections (mice). We have previously reported that roxithromycin increases the ability of human neutrophils (PMN) for bactericidal activity (S. aureus) or phagocytosis (K. pneumoniae) in vitro without altering other PMN functional parameters. In this study, roxithromycin (single dose-300 mg) was given to 6 human volunteers. The neutrophils collected 90 min after ingestion display a significant increased ability to phagocytose and kill S. aureus and K. pneumoniae. Furthermore chemotaxis, oxidative burst and myeloperoxidase activity of the PMN after roxithromycin ingestion were enhanced compared to those of PMN before ingestion. This discrepancy between immunomodulating effect of roxithromycin in vitro and in vivo outlines the complexity of in vivo experimental models and requires further studies in vivo in particular in patients suffering from sepsis.

Sera from 19 patients with scleroderma were tested for antilymphocyte antibodies (ALA) by indirect immunofluorescence assay. ALA were found in 47% of the cases when tested at 0 degrees, and in 27% at 25 degrees C. Anti-T cell specificity was shown after separation of B and T cells. The heterogeneity of the ALA detected was clear both among different patients and in serum from the same patient. A monoclonal antibody (UCHT1) inhibited ALA binding to T cells completely in one case, and partially in another three, implying that with these 4 sera, the lymphocyte receptors for ALA were either identical or very close to the UCHT1 receptor. This study defines another immunological abnormality in scleroderma: the presence of cold-reactive anti-T cell specific ALA. Their pathogenicity requires further investigation.

Certain tumor cells generate factors that inhibit neutrophil chemotaxis. The present study was designed to explore, in K-562 malignant cells, the release of such factors that may alter the neutrophil locomotion. The supernatant, separated from the K-562 malignant cells cultured in vitro for 48 hours, was lyophilised and extracted with ethanol 80%. This ethanol extract (SE-K562) inhibited neutrophil locomotion. Both random and locomotion induced either by formyl-methionyl-leucyl-phenylalanine (FMLP) or serum were inhibited. SE-K562 was partially purified by Sephadex chromatography and the analysis of the eluted active fraction by SDS electrophoresis led one band of about 8 kd. No one inhibitory effect was observed with appropriate controls. In conclusion, K562 malignant cells in culture release a low molecular weight factor (8 kd) that inhibits all forms of PMN locomotion i.e. random locomotion and locomotion induced either by FMLP or serum.

In order to counteract an ever increasing bacterial resistance, a new trend in antibiotic therapy is to try and obtain compounds with "immunostimulating" properties. Although the macrolides have been known for more than 30 years, their interaction with the host defence system has been poorly investigated. These drugs display an outstanding ability to penetrate and concentrate in phagocytes. Few depressive effects on phagocyte functions have been reported, while some macrolides have been shown to exert an immunostimulating effect in vitro and ex vivo. The data published on this subject are summarized in this review paper. Further studies would be required for a better understanding of structure-immunomodulating activity relationships.

Two bacterial strains (Staphylococcus aureus and Klebsiella pneumoniae) were exposed to subinhibitory concentrations of ceftriaxone. After an overnight culture in presence of 1 MIC of ceftriaxone either in broth or on solid medium S. aureus showed enlarged forms which were better phagocytosed (increase about 40%) and killed (increase about 50%) than control staphylococci. Exposure of K. pneumoniae to 0.1 MIC ceftriaxone resulted in filamentation of bacteria. When grown in the presence of 0.01 MIC, K. pneumoniae did not elongate into filaments but were significantly more phagocytosed (increase about 40%) or killed (increase about 170%) than control bacilli. The mechanism of the greater sensitivity to PMN killing of the altered S. aureus and K. pneumoniae was assessed either with phenylbutazone-treated PMN or by in-vitro exposure to crude granule extracts of PMN. The altered bacteria displayed a significant susceptibility to the non-oxidative killing mechanism while untreated bacteria were unaffected by the non-oxidative system. These data could explain the synergy observed between ceftriaxone and leucocytes in the killing of some micro-organisms.

Due to their high intracellular uptake, macrolides may interfere with phagocytes antibacterial system. We have studied the interaction of josamycin with bactericidal activity of human neutrophils (PMNs) or whole blood, in vitro. PMNs preincubated with josamycin (100-0.1 mg/l) display an increased phagocytic ability for K. pneumoniae, independently of the concentrations of josamycin; this effect appears to correlate with the recruitment of an additional population of phagocytizing PMNs without alteration of the mean number of PMN-associated bacteria, whatever the experimental conditions (adherent or non adherent PMNs). PMNs bactericidal function is also enhanced in the presence of josamycin in a dose-dependent manner (mean increase 60 to 370% for josamycin 0.1 to 10 mg/l). Bactericidal activity of whole human blood for P. aeruginosa (a strain resistant to the lytic effect of serum) is increased with a mean survival (CFUt min/CFU 0 min) of 24 and 71% at 60 and 120 min respectively, in the presence of josamycin 10 mg/l, and 42 and 128% in the presence of josamycin 1 mg/l, compared to the survival of the control, 68 and 166%. PMNs functions are not altered by josamycin with the exception of an enhancement of the oxidative burst induced by formylmethionyl-leucyl-phenylalanine, a synthetic compound similar to bacterial derivatives. In conclusion, we have shown a synergic interaction between phagocytes and josamycin for the killing of bacteria resistant to this antibiotic (MiC greater than 128 mg/l). This could be due either to an alteration of some PMN membrane receptors or to alterations of bacteria which render them more sensitive to natural bactericidal mechanisms and/or more able to activate these mechanisms.