Immunotoxic potential of N-ethyl, N-nitrosourea (ENU) in CD1 mice.

The immunotoxic potential of ENU, a potent and transplacental neurocarcinogen, was evaluated in male CD1 mice. The animals received i.p. injections of ENU--0, 2, 8 or 32 mg/kg body weight, in citrate-phosphate buffer, twice weekly for three weeks. Splenic lymphocytes were cultured in the presence of mitogens, lipopolysaccharide, pokeweed mitogen, concanavalin A and phytohaemagglutinin. Mixed lymphocyte cultures in the presence of allogeneic cells were also tested. Blastogenic response decreased in a dose-dependent manner, as measured by the 3H-thymidine uptake by splenocytes. Primary antibody production by splenic lymphocytes from animals challenged with a T-dependent antigen (sheep red blood cells) was stimulated at low doses but depressed at the highest dose group compared with the controls, whereas T-independent cell response showed no significant change. Our results suggest that exposure to repeated, low levels of ENU significantly alters the immune status of CD1 mice. The effects appear to be somewhat selective to T cell processes, based on in vivo responses to T-dependent and T-independent antigens.     

Synovial activation of chondrocytes: Evidence for complex cytokine interactions

Synoviocytes secrete factors which induce the synthesis of neutral metalloproteinases (NMP) and prostaglandin E₂ (PGE₂) by chondrocytes in a response called chondrocyte activation. We analyzed synovial chondrocyte activating factors (CAF) for the presence of cytokines which modulated the NMP production by articular chondrocytes. These studies suggested the presence of several other cytokines in addition to interleukin-1 (IL-1). Both resting and activated synoviocytes contained mRNA for basic fibroblast growth factor (bFGF) which is a synergist for IL-1 induced NMP production, and secreted bFGF into their culture media. They also expressed mRNA for transforming growth factor (TGF) which inhibits IL-1 induced NMP production. These cells also produce tumor necrosis factor (TNF) and trace amounts of interleukin-6 (IL-6). In addition to these there is evidence for a synovial activator of chondrocytes which is distinct from IL-1. Since a number of recombinant cytokines including TNF, IL-6 and bFGF failed to activate chondrocytes, this could be a novel cytokine.     

Enteric gram‐negative bacilli suppress Candida biofilms on Foley urinary catheters

Mixed Candida‐bacterial biofilms in urinary catheters are common in hospitalized patients. (i) The aims of this study were to evaluate, quantitatively and qualitatively, the in vitro development of mono‐ and dual‐species biofilms (MSBs and DSBs) of Candida albicans and two enteric gram‐negative bacilli (EGNB; Pseudomonas aeruginosa or Escherichia coli) on Foley catheter (FC) discs, (ii) to determine the biofilm growth in tryptic soy broth or glucose supplemented artificial urine (AU) and (iii) to assess the inhibitory effects of EGNB and their lipopolysaccharides (LPS) on Candida biofilm growth. The growth of MSBs and DSBs on FC discs was monitored by cell counts and SEM. The metabolic activity of LPS‐treated Candida biofilms was determined by the XTT reduction assay. Candida albicans and EGNB demonstrated significant inter‐ and intra‐species differences in biofilm growth on FC discs (p < 0.01). Pseudomonas aeruginosa suppressed Candida albicans significantly (p < 0.001) in DSBs. Compared with MSBs, DSB of EGNB in glucose supplemented AU demonstrated robust growth. Escherichia coli and its LPS, significantly suppressed Candida biofilm growth, compared with Pseudomonas aeruginosa and its LPS (p < 0.001). Candida albicans and EGNB colonization in FC is significantly increased in AU with glucose, and variably modified by Escherichia coli, Pseudomonas aeruginosa and their corresponding LPS.