In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes.

Interleukin-13 (IL-13) sequentially binds to IL-13Ralpha1 and IL-4Ralpha forming a high affinity signalling complex. This receptor complex is expressed on multiple cell types in the airway and signals through signal transducer and activator of transcription factor-6 (STAT-6) to stimulate the production of chemokines, cytokines and mucus. Antibodies have been generated, using the UCB Selected Lymphocyte Antibody Method (UCB SLAM), that block either binding of murine IL-13 (mIL-13) to mIL-13Ralpha1 and mIL-13Ralpha2, or block recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. Monoclonal antibody (mAb) A was shown to bind to mIL-13 with high affinity (K(D) 11 pM) and prevent binding of mIL-13 to mIL-13Ralpha1. MAb B, that also bound mIL-13 with high affinity (K(D) 8 pM), was shown to prevent recruitment of mIL-4Ralpha to the mIL-13/mIL-13Ralpha1 complex. In vitro, mAbs A and B similarly neutralised mIL-13-stimulated STAT-6 activation and TF-1 cell proliferation. In vivo, mAbs A and B demonstrated equipotent, dose-dependent inhibition of eotaxin generation in mice stimulated by intraperitoneal administration of recombinant mIL-13. In an allergic lung inflammation model in mice, mAbs A and B equipotently inhibited muc5ac mucin mRNA upregulation in lung tissue measured two days after intranasal allergen challenge. These data support the design of therapeutics for the treatment of allergic airway disease that inhibits assembly of the high affinity IL-13 receptor signalling complex, by blocking the binding of IL-13 to IL-13Ralpha1 and IL-13Ralpha2, or the subsequent recruitment of IL-4Ralpha.

Human Intestinal Schistosomiasis in Communities Living Near three Rivers of Jimma Town; South Western Ethiopia

BACKGROUND: Schistosoma mansoni is one of the parasites with high public and medical importance in Ethiopia. However; information is scarce about S. mansoni epidemiology in people living with higher risk of infection in Jimma town. This study was designed to determine point prevalence; intensity and risk factors of S. mansoni infection among residents nearby three rivers of Jimma town and assess the rate of Biomphalaria species shading cercariae from January to April; 2007. METHODS: A cross-sectional study was conducted in communities residing nearby three rivers of Jimma town. Structured questionnaires were used to collect data on socio- demographic and behavioral risk factors. After physical examination; stool samples were collected from 517 study participants and processed with Kato-Katz technique for microscopic examination and quantification of egg load. Snails were collected for identification of Biomphalaria species and then checked for cercarial shading. RESULTS: The prevalence of S. mansoni was 26.3with intensity ranging 24 to 936 eggs per gram of stool. Participants in the age group 10-19 years; OR = 2.19 (95CI; 1.10 - 4.34); and those living near the Awetu River; OR = 2.67 (95CI; 1.06 - 6.75); had higher risk of S. mansoni infection. Moreover; water contact while crossing a river; OR = 3.77 (95CI; 1.79 - 7.95); and swimming; OR = 2.59 (95CI; 1.37 - 4.91; was significantly associated with infection. Biomphalaria snails collected from Chore and Awetu Rivers shaded higher rate of cercariae compared with Kito River. CONCLUSION: A moderate prevalence of S. mansoni infection was shown in the study population. Infection rate among the residents correlated with rate of cercarial shading Biomphalaria snails. Treatment of targeted groups; appropriate health education and environmental measures (e.g. snail control) are needed to improve the situation