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The stability of cefodizime in five intravenous infusion fluids (0.9% sodium chloride, 5% dextrose in water, 10% dextrose in water, 5% amino acid injection, 3% polygeline) was studied at room temperature and at 4 degrees C. The compatibility of cefodizime with commonly used injectable drugs (ranitidine, metoclopramide, folinic acid, furosemide, aminophilline, methylprednisolone, betamethasone, hydrocortisone, dexamethasone, ketoprofen, noramidopyrine, acetylcysteine, digoxin, diazepam, acetylsalicylic acid, chlorpromazine, clonidine, clomipramine) was studied in 0.9% sodium chloride and 5% dextrose at room temperature. At intervals during the storage periods (up to 24 hrs at room temperature; up to 6 days at 4 degrees C) color, clarity and solution pH were examined; cefodizime content was determined by a microbiological method. Cefodizime concentrations remained greater than 90% of the initial concentrations in all infusion fluids for at least 24 hrs at room temperature and 6 days at 4 degrees C. No visual changes or appreciable changes in pH were observed for any of the solutions. Immediate clouding was observed when chlorpromazine was combined with the solution of cefodizime. A color change was observed when acetylcysteine was mixed with cefodizime. An increase in pH was noted when aminophilline was added to the solution of cefodizime. However, cefodizime concentrations remained greater than 90% of the initial concentrations of the solutions after mixture with all the tested drugs for at least 24 hrs at room temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphonuclear leukocytes (PMN) have been identified as cells capable of producing a number of pro- and antiinflammatory cytokines in response to specific agonists. Previously, we showed that tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), and IL-8, are produced by PMN after stimulation with agonists, such as lipopolysaccharide (LPS). In this study, we demonstrate that LPS is also a potent stimulus for the mRNA expression and release of the IL-1 receptor antagonist (IL-1ra). In addition, we show that the release of IL-1ra from LPS-stimulated PMN is markedly potentiated in the presence of IL-10 (from two to threefold after 18 h of stimulation). Moreover, we observed that this upregulation of IL-1ra production by IL-10 in LPS-stimulated PMN took place through IL-1ra mRNA stabilization. Indeed, the half-life of IL-1ra mRNA was prolonged in PMN stimulated in the presence of IL-10 and LPS, as compared with cells stimulated with LPS alone. That IL-10 selectively upregulates IL-1ra production in LPS-activated PMN, while it inhibits the production of IL-1 beta, TNF, and IL-8 under the same conditions, suggests that IL-10 may be an important physiologic regulator of cytokine production from PMN, and emphasizes the potential role of IL-10 in inflammatory responses.

In this study we have examined the effects of interleukin 10 (IL-10) on polymorphonuclear leukocytes (PMN), and found that it is a potent inhibitor of tumor necrosis factor (TNF), IL-1 beta, and IL-8 secretion triggered by lipopolysaccharide (LPS). Cytokine production by phagocytosing PMN was also inhibited by IL-10, but to a lesser extent than the LPS-induced production. As shown by Northern blot analysis, IL-10 diminished the levels of TNF, IL-1 beta, and IL-8 mRNAs late after the onset of stimulation of PMN with LPS. In addition, we provide evidence that the kinetics of LPS-induced IL-8 production by PMN is composed of two distinct phases. Specifically, our experiments demonstrated that in the first phase, the production of IL-8 is a process directly induced by LPS that lasts for some hours. After this early wave, a second phase begins that is sustained and leads to an elevated production of IL-8 that appears to be due to the endogenous release of TNF and IL-1 beta. This second wave can in fact be blocked by anti-TNF and anti-IL-1 beta neutralizing antibodies, and by IL-10 as the consequence of its downregulatory effects on TNF and IL-1 beta release. Taken together, these findings identify novel biological actions of IL-10 as a suppressor of the inflammatory response.