A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs

Evaluation of skin sensitivity after shock wave treatment in horses

Objective: To evaluate the effects of shock wave treatment on cutaneous nerve function, compared with the effects of local nerve block and sedation. Animals: 18 clinically sound Swiss Warmbloods. Procedure: Horses were randomly allocated to 3 groups and received different amounts and types of shock waves (extracorporeal shock wave treatment [ESWT] or radial pressure wave treatment [RPWT]). Horses were sedated with xylazine and levomethadone. Shock waves were applied to the lateral palmar digital nerve at the level of the proximal sesamoid bones on 1 forelimb. Skin sensitivity was evaluated by means of an electrical stimulus at the coronary band before and 5 minutes after sedation and at 4, 24, and 48 hours after application of ESWT or RPWT. On the contralateral forelimb, skin sensitivity was tested before and 10 minutes after an abaxial sesamoid nerve block. Results: No significant changes in skin sensitivity were detected, regardless of the shock wave protocol applied. Mean reaction thresholds after sedation were more than twice the baseline thresholds. After the abaxial sesamoid block, no reaction was recorded in any of the horses. Conclusions and Clinical Relevance: Application of ESWT or RPWT to the palmar digital nerve had no effect on cutaneous sensation distal to the treated region for at least 2 days after application. The analgesic effect of sedation on reaction to electrical stimuli was distinct but varied among horses