Gamma interferon is shown to be critical in recovery of C57BLU6 mice from mousepox. Anti-gamma interferon treatment of mice infected in the footpad with ectromelia virus resulted in enhanced spread to and efficient virus replication in the spleen, lungs, ovaries, and, especially, liver. All treated, infected mice died within a mean of 7 days, 2.5 days earlier than mice with severe combined immunodeficiency that were given a comparable infection. On the other hand, alpha interferon appeared not to have a major role in controlling virus replication in tissues examined, and beta interferon was important for virus clearance in the liver and ovaries but not the spleen. Either anti-alpha, beta interferon or anti-beta interferon antibody therapy resulted in only 25% mortality. Infected control mice survived but showed persistence of ectromelia virus at the site of infection (the footpad) and transient presence of the virus in the spleen, liver, lungs, and ovaries and in the fibroreticular but not lymphoid cells of the draining popliteal lymph node. Depletion of gamma interferon but not alpha and/or beta interferon resulted in a significant reduction in the numbers of splenic T (especially 'y8-TCR+), B, and Mac-l+ cells, although the proportion of Mac-l+ cells in the spleen increased compared with control values. Depletion of alpha, beta, or gamma interferons did not severely affect the generation of virus-specific cytotoxic T-lymphocyte responses or natural killer cell cytolytic activity. This study, in which a natural virus disease model was used, underscores the crucial importance of gamma interferon in virus clearance at all stages of infection and in all tissues tested except the primary site of infection, where virus clearance appears to be delayed.

1 Release-modulating opioid and cannabinoid (CB) receptors, b-adrenoceptors and bradykinin receptors at noradrenergic axons were studied in mouse tissues (occipito-parietal cortex, heart atria, vas deferens and spleen) preincubated with 3 H-noradrenaline. 2 Experiments using the OP 1 receptor-selective agonists DPDPE and DSLET, the OP 2 -selective agonists U50488H and U69593, the OP 3 -selective agonist DAMGO, the ORL 1 receptor-selective agonist nociceptin, and a number of selective antagonists showed that the noradrenergic axons innervating the occipito-parietal cortex possess release-inhibiting OP 3 and ORL 1 receptors, those innervating atria OP 1 , ORL 1 and possibly OP 3 receptors, and those innervating the vas deferens all four opioid receptor types. 3 Experiments using the non-selective CB agonists WIN 55,212-2 and CP 55,940 and the CB 1 -selective antagonist SR 141716A indicated that the noradrenergic axons of the vas deferens possess release-inhibiting CB 1 receptors. Presynaptic CB receptors were not found in the occipito-parietal cortex, in atria or in the spleen. 4 Experiments using the non-selective b-adrenoceptor agonist isoprenaline and the b 2 -selective agonist salbutamol, as well as subtype-selective antagonists, demonstrated the occurrence of releaseenhancing b 2 -adrenoceptors at the sympathetic axons of atria and the spleen, but demonstrated their absence in the occipito-parietal cortex and the vas deferens. 5 Experiments with bradykinin and the B 2 -selective antagonist Hoe 140 showed the operation of release-enhancing B 2 receptors at the sympathetic axons of atria, the vas deferens and the spleen, but showed their absence in the occipito-parietal cortex.6 The experiments document a number of new presynaptic receptor locations. They con®rm and extend the existence of marked tissue and species dierences in presynaptic receptors at noradrenergic neurons.

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