ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion is ICOS dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s, was significantly reduced after lung injury in ICOS-/- mice, and strikingly, treatment with IL-5 protected both ICOS-/- and wild-type mice from mortality. These results imply that low ICOS expression and decreased lung ILC2s in IPF patients may contribute to poor recovery from infections and acute exacerbation and that IL-5 treatment may be a novel therapeutic strategy to overcome these defects and protect against lung injury.

Antibacterial Co(II), Cu(II), Ni(II) and Zn(II) Complexes of Thiadiazoles Schiff Bases.

Schiff bases were obtained by condensation of 2-amino-l,3,4-thiadiazole with 5-substituted-salicylaldehydes which were further used to obtain complexes of the type [M(L)(2)]Cl(2), where M=Co(II), Cu(II), Ni(II) or Zn(II). The new compounds described here have been characterized by physical, spectral and analytical data, and have been screened for antibacterial activity against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of these Schiff bases increased upon chelation/complexation, against the tested bacterial species, opening new aproaches in the fight against antibiotic resistant strains.

Synthesis, Characterization and Biological Evaluation of Co(II), Cu(II), Ni(II) and Zn(II) Complexes With Cephradine.

Some Co(II), Cu(II), Ni(II) and Zn(II) complexes of antibacterial drug cephradine have been prepared and characterized by their physical, spectral and analytical data. Cephradine acts as bidentate and the complexes have compositions, [M(L)(2)X(2)] where [M = Co(II), Ni(II) and Zn(II), L = cephradine and X = Cl(2)] showing octahedral geometry, and [M(L)(2)] where [M = Cu(II), L = cephradine] showing square planar geometry. In order to evaluate the effect of metal ions upon chelation, eephradine and its complexes have been screened for their antibacterial activity against bacterial strains, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.

Immunity in hepatitis C infection.

Polymerase chain reaction (PCR) and newer serologic assays for hepatitis C virus (HCV) were used to investigate 19 HCV cross-challenge episodes in chimpanzees. In these cross-challenges, 59% showed seroconversion after challenge, 33% showed reappearance of HCV-associated hepatocellular ultrastructural changes, 5 animals not PCR-positive at the time of challenge showed return of PCR positivity, and 26% developed hepatitis after rechallenge. A total of 74% showed at least one of these signs of reinfection. The frequency of development of serologic and ultrastructural responses was, however, reduced in secondary compared with primary infections (P less than .01). In 10 animals, the cross-challenge was done with heterologous strains, and in 9 with the originally infecting virus. There was no significant difference in the responses to homologous and heterologous challenges. The data suggest relatively weak immunity in HCV infections.