9.      Hair growth modulatory properties of IL-6 cytokine family members.  
Kevin McElwee(1), Mei Yu(1), Vivian Lu(1), Blanche Lo(1), Jerry Shapiro(1), Pia Freyschmidt-Paul(2), Sabine Kissling(2), Rolf Hoffmann(3). 1. Dept. Dermatology, University of British Columbia, Vancouver, Canada; 2. Dept. Dermatology, Philipp University, Marburg, Germany, 3.Dermaticum, Freiburg, Germany

The activation of receptor complexes containing glycoprotein 130 (gp130) identifies the IL-6 cytokine family. We examined members of this family, Interleukin-6 (IL-6), interleukin-11 (IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1) in hair follicles. Quantitative RT-PCR using mRNA derived from microdissected, anagen stage, human hair follicles and comparison to non-follicular skin epithelium revealed mRNA for IL-6 and OSM as the most highly expressed while IL-11r, OSMr and CNTFr were the most highly expressed receptors of the evaluated group. Immunohistology suggested expression of IL-6, LIFr and IL-11r in the root sheaths and dermal papilla, while OSM and IL-11, IL-6r and OSMr were expressed in root sheaths alone. CT-1 and LIF demonstrated little if any presence. The gp130 receptor subunit was located in the dermal papilla, root sheaths, hair cuticle and matrix. Human hair follicles from 5 donors were exposed in vitro to 0.1, 1, 10, or 100 ng/ml of OSM or CT-1 for 8 days. Compared to control hair follicles, OSM and CT1 exhibited a growth inhibition capacity. OSM and CT-1 incubated with agarose beads and injected subcutaneously at 1ìg per mouse into telogen skin of mice all 65 days old revealed no capacity to induce anagen hair growth. In contrast, injection of 65 day old mice in which anagen had been induced by hair plucking revealed a hair growth inhibitory capacity for OSM but no significant effect for CT1. The data identify IL-6 cytokine family members as modulators of hair follicle growth. High expression of IL-6 cytokine family members can occur as a constituent of skin or hair follicle inflammation such as alopecia areata. In principle, increased expression in cutaneous inflammation may contribute to the promotion of hair loss. The nature of expression distribution circumstantially suggests a role in hair follicle keratinocyte differentiation.