Individualizing the risk/benefit ratio of NSAIDs in older patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have provided safe, effective relief of pain and inflammation in millions of elderly patients. Their role in the therapy of rheumatic disease, particularly in helping patients to maintain an independent lifestyle, is indisputable. Despite this success, recent epidemiologic studies have confirmed an increased relative risk for a wide variety of significant toxicities. Advanced age has emerged as one of the most striking risk factors for all of the commonly associated side effects. However, considering the large proportion of the population using these drugs, the absolute risk is remarkably low. Recognizing those elderly individuals most likely to benefit and least likely to suffer from NSAID use is the key to their appropriate use.

Bacterial lipopolysaccharide-induced immunoglobulin synthesis by human blood lymphocytes partially depleted of monocytes.

Bacterial lipopolysaccharide (LPS), a potent polyclonal B cell activator in rodents has not been found to be a consistent activator of human peripheral blood mononuclear cells (PBM). Since LPS activates monocytes to become suppressor cells, we asked whether depletion of monocytes would enhance the ability of LPS to induce in vitro activation and immunoglobulin synthesis and secretion by human B lymphocytes. Addition of 50 micrograms/ml LPS for 7 days to PBM cultures failed to induce a significant increase in IgM and IgG synthesis as measured by radioimmunoassay of culture supernatants. However, after partial depletion of adherent cells, the non-adherent cell population (NAC) produced large amounts of IgM and IgG (IgM: 696 ng/10(6) PBM vs 4236 ng/10(6) NAC, P less than 0.005; IgG: 68 ng/10(6) PBM vs 922 ng/10(6) NAC, P less than 0.02). The LPS-induced response was found to be T cell dependent and could be readily suppressed by the addition of autologous adherent cells. Addition of indomethacin to LPS-stimulated PBM did not result in increased Ig secretion. The poor response of human blood B cells to LPS may be due to the suppressive effect of activated monocytes.