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AIDS is known to cause a shift of cytokines in the periphery. However, predominant cytokines in skin of patients with HIV-associated skin diseases have not been clearly defined. We hypothesized that there are distinct cytokine profiles that distinguish among the different clinical manifestations of AIDS-related skin diseases. To test this hypothesis, lesional and non-lesional skin was biopsied from 53 HIV+ patients with Kaposi's sarcoma (KS), psoriasis, and pruritus due to eosinophilic folliculitis, and from HIV negative controls with psoriasis or KS prior to therapy. Immunohistochemistry was performed with antibodies to tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon (IFN)-gamma, and interferon-inducible protein (IP)-10. HIV positive individuals included 10 with psoriasis, 14 with pruritus, and 15 with Kaposi's sarcoma. HIV negative controls included 12 with psoriasis and two with KS. Semi-quantitative analysis of cytokine staining was confirmed by optical density using a digital imaging system on four representative skin sections from each disease. Optical density analyses were conducted using ANOVA and t-tests. We found that epidermis overlying HIV+ Kaposi's sarcoma was hyperproliferative and was highest in IP-10, IFN-gamma, and IL-10 (P=0.0001). HIV+ pruritus was significantly highest in TNF-alpha (P=0.0001) staining. HIV+ psoriasis represented an intermediate state for all four cytokines. Normal skin adjacent to lesions showed the same relative patterns, with lower intensities. Skin diseases seen frequently in the setting of HIV and immunodeficiency have relatively distinct levels and patterns of cytokine expression that may reflect immune dysfunction, reactivity to HIV and to opportunistic infections.

Human eosinophils secrete two distinct ribonucleases that have antiviral activity against pathogens of the family Paramyxoviridae. To examine the role of eosinophils and their ribonucleases in host defense against paramyxovirus pathogens in vivo, we have developed a mouse model involving a viral pathogen that naturally targets a rodent host. In this work we describe infection of Balb/c mice with pneumonia virus of mice (PVM, strain J3666), a paramyxovirus pathogen found frequently among rodent populations. We show here that pulmonary eosinophilia is an immediate response to infection with PVM, with bronchoalveolar lavage fluid containing 12-14% eosinophils obtained as early as day 3 postinoculation. Infection is accompanied by the production of macrophage inflammatory protein-1-alpha (MIP-1alpha), a chemokine that has been associated with the pulmonary eosinophilia observed in response to respiratory syncytial virus infection in humans and with enhanced clearance of influenza virus in mice. Interestingly, we observed no changes in expression of the chemoattractants eotaxin and RANTES in response to PVM infection, and interleukin-5 remained undetectable throughout. These responses-clinical pathology, viral recovery, pulmonary eosinophilia, and production of MIP-1alpha-will provide a means for exploring the role of eosinophils, eosinophil secretory ribonucleases, and eosinophil chemoattractants in host defense against PVM and related paramyxovirus pathogens in vivo., (Copyright 2000 Academic Press.)

We describe a case of early human immunodeficiency virus infection characterized by transient eosinophilia without an elevated immunoglobulin E concentration, allergic symptoms, or atopic dermatitis. Possible mechanisms of the eosinophilia are discussed.

Eosinophilic folliculitis (EF) is a chronic, intensely pruritic condition of unknown pathogenesis that causes marked morbidity in those HIV patients whom it affects. There is a wide differential diagnosis of itchy skin conditions in HIV which are amenable to different treatments. It is therefore essential to take a biopsy of each suspected case and examine multiple sections of the biopsy to confirm or refute a diagnosis of EF. Treatment of EF can be difficult but we hope that by suggesting a rational approach to this and considering possible therapeutic options more patients may be helped with this troublesome dermatosis.

The attachment glycoprotein G of respiratory syncytial virus (RSV) is produced as both membrane-anchored and secreted forms by infected cells. Immunization with secreted RSV G (Gs) or formalin-inactivated alumprecipitated RSV (FI-RSV) predisposes mice to immune responses involving a Th2 cell phenotype which results in more severe illness and pathology, decreased viral clearance, and increased pulmonary eosinophilia upon subsequent RSV challenge. These responses are associated with increased interleukin-4 (IL-4) production in FI-RSV-primed mice, and the responses are IL-4 dependent. RNase protection assays demonstrated that similar levels of IL-4 mRNA were induced after RSV challenge in mice primed with vaccinia virus expressing Gs (vvGs) or a construct expressing only membrane-anchored G (vvGr). However, upon RSV challenge, vvGs-primed mice produced significantly greater levels of IL-5 and IL-13 mRNA and protein than vvGr-primed mice. Administration of neutralizing anti-IL-4 antibody 11.B11 during vaccinia virus priming did not alter the levels of vvGs-induced IL-5, IL-13, pulmonary eosinophilia, illness, or RSV titers upon RSV challenge, although immunoglobulin G (IgG) isotype profiles revealed that more IgG2a was produced. vvGs-priming of IL-4-deficient mice demonstrated that G-induced airway eosinophilia was not dependent on IL-4. In contrast, airway eosinophilia induced by FI-RSV priming was significantly reduced in IL-4-deficient mice. Thus we conclude that, in contrast to FI-RSV, the secreted form of RSV G can directly induce IL-5 and IL-13, producing pulmonary eosinophilia and enhanced illness in RSV-challenged mice by an IL-4-independent mechanism.

In BALB/c mice, sensitization with the attachment protein (G) of respiratory syncytial virus (RSV) leads to CD4+ T cell-mediated lung eosinophilia during subsequent challenge with RSV. To determine the host genetic influences on this model of lung eosinophilia, we tested 15 different inbred mouse strains. Eosinophilia developed in all H-2d (BALB/c, DBA/2n, and B10.D2), but not in H-2k (CBA/Ca, CBA/J, C3H, BALB.K, or B10.BR) mouse strains. Among H-2b mice, 129 and BALB.B developed eosinophilia, whereas C57BL/6 and C57BL/10 did not. Testing first generation crosses between sensitive and resistant strains showed that eosinophilia developed in all H-2dxk (n = 5), irrespective of background genes, but not in H-2dxb (n = 2) mice. In vivo depletion of CD8+ T cells or IFN-gamma rendered C57BL/6, but not BALB.K mice, susceptible to eosinophilia. Analysis of B10 recombinant mice showed that the Dd allele (in B10.A(5R) mice) prevented CD8+ T cell accumulation in the lung, resulting in intense lung eosinophilia. However, the Db allele (in B10.A(2R) and B10.A(4R) mice) supported CD8+ T cell expansion and prevented eosinophilia. Intracellular cytokine staining showed that lung eosinophilia correlated with reduced IFN-gamma and increased IL-10 expression in lung T cells. These results are compatible with the unifying model that Th2 cells mediate the disease but can be inhibited by CD8+ T cells secreting IFN-gamma. Our findings have important implications for the development of protective, nonpathogenic vaccines for RSV disease.

The term HIV-associated eosinophilic folliculitis (EF) designates an idiopathic dermatitis that appears in HIV-infected patients with different clinical manifestations but with a distinctive histological feature characterized by a predominantly eosinophilic infiltrate in the follicular infundibula. On the other side, follicular mucinosis (FM) is a reaction pattern in the follicular epithelium, characterized by a mucinous degeneration of the outer sheath of follicles and sebaceous glands. It has been described in association with a variety of unrelated conditions. We report 2 HIV-infected patients with a pruritic papular eruption. Histopathological study revealed the coexistence of EF and FM. To our knowledge, this is the first report that describes this association. The possible relationship between these two entities is discussed.