Pharmacological effect of hyaluronic acid (HA) on phagocytes: hypothesis for an HA-induced monocyte chemotactic factor for neutrophils.

The connection between hyaluronic acid and phagocyte function is not well documented in the literature. Its action may either inhibit or enhance polymorphonuclear neutrophil (PMN) function, depending on its concentration. Studies were conducted to verify the effect of hyaluronic acid on phagocytes, both directly using hyaluronic acid and indirectly via a mediated route using the medium from a hyaluronic acid monocyte incubation. Determinations were made of phagocytosis, reduction of nitroblue tetrazolium, superoxide production, and chemotaxis before and after incubation with hyaluronic acid. Chemotaxis of PMNs was used to evaluate the chemotactic action of a medium in which monocytes had been incubated with hyaluronic acid. This method resulted in progressive improvement in the chemotactic index. The authors conclude that the monocytes incubated with hyaluronic acid produce a chemotactic factor for neutrophils.

[Effect of methisoprinol on neutrophil functions in patients with rheumatoid arthritis]. / Effetto del metisoprinolo sulle funzioni dei neutrofili in pazienti affetti da artrite reumatoide.

Neutrophils and monocytes are fundamental to the inflammatory process. They migrate into inflammatory foci where they manufacture and release numerous substances (enzymes X O2 ions) which if not controlled may injure the tissues they come in contact with. This enhanced response is responsible for the degenerative reaction typical of inflammation which occurs in rheumatoid arthritis. neutrophil and monocyte metabolism are activated in response to various drugs or to chemicals that may be produced either by the inflammatory agents or by other immunocompetent cells. Hence, immune system modulators may be employed to control their response. For this reason neutrophil and monocyte function was studied in subjects with rheumatoid arthritis as was the ability of methisoprinol, a major immunomodulating drug, to control their functional response both in vivo and in vitro. Neutrophils present a defective chemotactic activity attributable to a circulating inhibitory factor, a defect that methisoprinol can correct. The drug also stimulates lymphocytes and monocytes to produce substances that activate neutrophil chemotaxis. Methisoprinol is an excellent drug that can modify the altered cell-mediated immunity of rheumatoid arthritis patients.

[Importance of hyaluronic acid in the modulation of neutrophil migration]. / Importanza dell'acido ialuronico nel modulare la migrazione dei neutrofili.

The relationship between JA and phagocyte function has often been reported in the literature. The action of JA may either inhibit or stimulate PMNs function depending on the concentration. On the basis of this experience, the efficacy of JA action, both directly and mediated after incubation was studied. In particular phagocytosis, NBT, superoxide production and chemotaxis were studied in basal conditions and after incubation with hyaluronic acid. In particular chemotaxis was also performed to assay the chemotactic action of the medium in which the monocytes were incubated with JA and the technique was found to produce a distinct progressive improvement in the chemotactic index. In conclusion, it is hypothesised that monocytes incubated with JA produce a chemotactic factor for PMNs.

Assessment of lymphocyte and phagocytic cell function in healthy volunteers undergoing short-term phenytoin administration.

The effect of short-term (2 weeks) administration of the anticonvulsant drug phenytoin on humoral and cellular immune function and phagocytic cell system activity was tested in nine healthy volunteers. No change either in the absolute or relative counts of leukocytes was found after drug treatment. Moreover, immunoglobulin serum concentration and lymphocyte subsets positive for OKT3, OKT4, OKT8, OKDRIA, OKB2, Leu 7, Leu 11a, anti-beta 2-microglobulin and antitransferrin monoclonal antibodies were not affected by phenytoin administration. A significant impairment of both polymorphonuclear neutrophil migrating activity and stimulated metabolism as measured by nitro blue tetrazolium reduction and superoxide anion generation was found after drug treatment or when phenytoin was added in vitro to the cells at concentrations lying within the anticonvulsant therapeutic range. Monocyte function was unaffected both after phenytoin administration and after direct application to the cells. The phenytoin-induced changes of polymorphonuclear neutrophil function was completely reverted within 2 weeks after drug withdrawal. The phenytoin-induced alterations of the phagocytic cell system are discussed in relation not only to the possible implications in the pathogenesis of adverse effects of anticonvulsant therapy but also to the potential therapeutic exploitation in immunologically mediated disorders.