Cohabitation with an Ehrlich tumor-bearing cagemate induces immune but not behavioral changes in male mice.

Cohabitation with Ehrlich ascitic tumor-injected conspecifics induces behavioral, neurochemical, endocrine and immune changes indicative of stress and immune impairment in female mice. The present work analyzed the effects of similar cohabitation in Swiss and Balb/C male mice. At least 12 pairs of male mice were divided into a control group and an experimental group. On experimental day 1 (ED1), one animal within each experimental pair was inoculated with 5×106 Ehrlich tumor cells intraperitoneally (i.p.); the other animal was kept undisturbed and was referred to as the CSP (companion of a sick partner). One male mouse of each control pair was treated i.p. with 0.9% NaCl (1mL/kg); the other animal (the CHP, companion of a healthy partner) was kept undisturbed. Cohabitation with a sick partner for 11days did not induce any behavioral, hypothalamic noradrenergic, corticosterone or adrenal weight changes in the Swiss CSP male mice compared to those of the Swiss CHP group. However, impairments in neutrophil phagocytosis and oxidative burst as well as increased levels of catecholamines were observed in Swiss and Balb/C CSP mice relative to CHP male animals of the same strains on ED11 and ED14, respectively. Moreover, after a challenge with 5×106 Ehrlich tumor cells on ED11 of cohabitation, the number and concentration of tumor cells found in the ascitic fluid were higher in the Swiss CSP male mice than in the CHP mice. These data suggest that the immune changes observed in Swiss and Balb/C male CSP mice after cohabitation with a sick cagemate might, ultimately, depend on the changes induced by catecholamines, as previously reported for CSP female mice. However, contrary to that reported in Swiss CSP female mice, changes in behavioral and hypothalamic noradrenaline activity were not found in the Swiss CSP male mice analyzed in this work. This fact suggests that male and female CSP mice might use similar immune but different CNS strategies against the threats posed by the tumor-bearing animals.

Induction of chicken cytokine responses in vivo and in vitro by lipooligosaccharide of Campylobacter jejuni HS:10.

Campylobacter jejuni is a pathogen of the gastrointestinal tract of humans, but colonizes chickens for prolonged periods without causing disease. It is unclear what host and bacterial mechanisms maintain a non-inflammatory state in chickens. The present work was undertaken to characterize cytokine responses of chickens to purified lipooligosaccharide (LOS) of C. jejuni HS:10. Chickens were injected with purified LOS, and expression of interleukin (IL)-1ß (pro-inflammatory cytokine), IL-8 (pro-inflammatory chemokine), interferon (IFN)γ (Th1-like cytokine), IL-10 (immune regulatory/anti-inflammatory cytokine) and IL-13 (Th2-like cytokine) was evaluated in spleen using quantitative RT-PCR, up to 24h post-injection. In an in vitro study, splenocytes were incubated with LOS, and cytokine expression followed up to 18 h. Chickens injected with LOS had increased expression of IL-1ß up to 24h later. Expression of IL-8 was significantly increased at 2h but then declined below baseline. Expression of IFNγ and IL-10 was increased significantly at 2h, but declined thereafter. Splenocytes incubated with LOS had increased expression of IL-1ß and IL-8 up to 18 h of incubation. Expression of IFNγ was increased at 6 and 18 h, IL-10 was increased at 2h, but expression of IL-13 did not differ significantly up to 18h. It is concluded that LOS of C. jejuni can induce expression of pro-inflammatory IL-1ß and IL-8, as well as IFNγ and IL-10 in chickens. More extensive studies with more prolonged exposure to LOS are needed to further clarify the interaction between C. jejuni and the chicken host.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor.