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Interleukin-1 receptor antagonist-deficient (Il1rn-/-) BALB/c mice developed inflammation localized to the skin of the ear pinna in 64% of the cases examined. Histopathologically, the disease had many features resembling human psoriasis, suggesting that it might be a useful disease model. The epidermis became thickened and hypertrophic, and expressed the immature keratin, K6, throughout. The stratum corneum showed parakeratotsis. Large epidermal projections formed into a grossly thickened dermis and both tissues were infiltrated by leukocytes. Neutrophil-rich microabscesses formed beneath the stratum corneum. Dendritic cells and activated T cells of both helper classes were identified in both the dermis and epidermis, while a high density of macrophages was seen in the dermis, where mast cells were also prominent. Dense patterns of apparently activated small dermal vessels were seen in the diseased dermis. Cutaneous inflammation, along with arterial inflammation and arthritis, is the third site-specific, inflammatory disease to be found to affect Il1rn-/- BALB/c mice. None of the diseases affected Il1rn-/- C57BL/6. In F2 hybrids of Il1rn-/- BALB/c and C57BL/6, cutaneous inflammation was absent, aortic inflammation was common, and arthritis was rare, indicating that the sets of background modifier genes that cause susceptibility to each disease are not fully overlapping.

Using matrices based upon Affi-Gel and Affi-Prep, we have examined conditions during the immobilization of antibodies (immunoglobulin G, IgG) that influence the performance of immunosorbents. Such conditions include: coupling pH, coupling kinetics, antibody density on the immunosorbent and the activation chemistries utilized for the immobilization process. These studies have shown that the capacity for antigen does not increase with increased antibody coupling efficiency. Presumably, increased coupling times or efficiencies lead to multi-site attachment of the antibody to the matrix, thereby causing inactivation. Immunosorbents containing low densities of IgG were found to have greater capacity for antigen on a per mole IgG basis. This suggests steric crowding of antigen at high antibody density. Finally, immunosorbents prepared through IgG carbohydrate linkages (oriented coupling) show dramatic increases in antigen capacity over those prepared by stochastic (random) coupling through IgG primary amino groups. A combination of low IgG density and oriented coupling of the IgG via the carbohydrate moiety may represent the best strategy for the preparation of immunosorbents.