Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells.

The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5-fold increase in the number of myeloid colony-forming units (CFU-C) was observed when bone marrow cells were cultured in the presence of conditioned medium prepared from nonadherent mononuclear cells cultured with 10(-4) M histamine (CM-histamine) compared with phosphate-buffered saline (CM-PBS). Using ELISA and radioimmunoassay kits, histamine was found to enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and anti-IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the blocking effect in CM-histamine was moderate, indicating enhanced GM-CSF and IL-6 activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM-histamine or CM-PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation of CM-histamine with H1 and H2 receptor antagonists resulted in complete blocking of the histamine-enhanced colony-stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM-CSF and IL-6 via H1 and H2 receptors.

In vitro cell-mediated immunologic assay for cow's milk allergy.

The production of a lymphokine, the leukocyte-migration-inhibition factor (LIF), by peripheral blood lymphocytes in response to an in vitro challenge with bovine beta-lactoglobulin was assayed in infants and children suspected of having allergy to cow's milk protein. Of the patients studied, 24 had cow's milk allergy, 24 were normal control subjects, 18 had recovered from milk allergy, 10 were newborns, and 10 were babies suffering from acute gastroenteritis. All patients with milk allergy demonstrated significant LIF production in response to beta-lactoglobulin (23.5% +/- 6.4%). In the normal control subjects, LIF was 3.1% +/- 4.3% (P < .0005). Only two of the 24 control subjects and two of the ten newborns had high-normal values bordering on the positive. None of the ten babies with acute gastroenteritis gave a positive response. Most of the children who had recovered from milk allergy and were ingesting cow's milk had negative assays. This cell-mediated immune assay is shown to be a reliable test for the diagnosis of sensitivity to milk protein in infants and children, and for determining dietary treatment and when this treatment can be safely terminated. In most cases, its use should eliminate the need for the potentially dangerous and ethically questionable provocation test, as well as the need for repeated intestinal biopsies.

Autoantibodies in male homosexuals and HIV infection.

We have used ELISA to study the frequency of autoantibodies to several antigens in the serum of 17 male homosexuals (MHS) negative for HIV (HIV-), 11 asymptomatic HIV seropositive MHS (HIV+) and patients with ARC (N = 15) or AIDS (N = 13), and compared them to 20 matched healthy heterosexual controls. Serum antibody binding to histones, cardiolipin, ss-A, ss-B and Sm was found to be significantly higher in each of the MHS groups studied as compared to controls (P less than 0.001), and was also increased in the HIV+ patients vs. the HIV- group (P less than 0.05). In contrast, no increase in autoantibodies to ss-DNA, ds-DNA, poly(I), poly(G) or RNP were found in any of the groups tested. These results enlarge the spectrum of autoimmunity previously reported in HIV infection and identify a similar pattern to a lesser degree, already present in HIV- MHS, suggesting a role for HIV or concomitant virus infections in its pathogenesis.

Activated interferon system in healthy homosexual men.

More than 50% of a group of healthy homosexuals in Israel were found to have an activated interferon (IFN) system as evidenced by markedly elevated blood IFN levels, increased in vitro production of IFN by unstimulated peripheral blood mononuclear cells and HuIFN-alpha and HuIFN-gamma production by appropriately stimulated cells, and a surprisingly high incidence of an antiviral state of cells. This pattern resembles that found in persons with acute viral illness, and is unlike that found in normal healthy controls. The type of IFN in the blood was found to be unusual in that it was mainly HuIFN-alpha, pH 2-labile, a type of IFN found in certain collagen diseases as well as in homosexual men suffering from Kaposi's sarcoma or lymphadenopathy. Natural killer (NK) cytotoxic activity was found to be somewhat lower than that found in normal controls, although no correlation was found between blood IFN levels and NK activity. Mean (2'-5')-oligoisoadenylate synthetase levels in cell extracts were intermediate between normal controls and patients with viral illness. Likewise no correlation was found between enzyme levels and blood IFN levels. The highly activated IFN system found in certain homosexuals, as well as the increased spontaneous production of IFN by unstimulated mononuclear cells, suggest the possibility of the presence of a virus, active or latent, in these individuals. This virus could be a retrovirus such as HTLV-III or LAV which have recently been isolated from AIDS patients. The special type of IFN present could be the response to a novel virus in an unusual situation. On the basis of recent reports, we speculate that homosexuals with highly activated IFN systems who produce pH 2-labile HuIFN-alpha could be at increased risk for developing AIDS.

Immune derangements in asymptomatic male homosexuals in Israel: a pre-AIDS condition?

We have described several immune derangements found in a clinically asymptomatic group of 117 male homosexuals (MHS) in Israel. These consisted of a marked decrease in TH and TS cells, decreased NK and allogeneic response, and increased levels of acid labile alpha-interferon and circulating immune complexes (CIC). Most of these alterations were found in approximately 40% of the subjects, with no simple correlation between them. Since Israel is a low incidence area for AIDS and related syndromes, it is suggested that this situation reflects a common situation among asymptomatic MHS in general, although the reasons for these impairments are not clear. This situation may therefore explain susceptibility of the male homosexual for developing AIDS, given the appropriate circumstances, environment, and genetic background.

Cell mediated immunity and effects of "thymic humoral factor" in 15 patients with SSPE.

Cell mediated immunity (CMI) in 15 patients with subacute sclerosing panencephalitis (SSPE) was assessed by E-rosette formation, leucocyte migration inhibition factor (LIF) production, and proliferative responses to mitogens. In eleven patients, one or more of these parameters were impaired. These defects varied among the different patients and no consistent or uniform pattern of immune deficiency could be demonstrated. Although no single patient had a generalized reduction of all the T-cell functions, a diminished percentage of E-rosetting cells was the most frequent abnormal parameter (7 out of 15 patients). There was no correlation between the clinical state of the patients and the immune defects. Thymic humoral factor (THF), a thymic hormone, reconstituted at least one CMI impaired function especially the reduced levels of E-rosette forming cells in 7 out of 9 patients. It seems unlikely that a generalized cell-mediated defect is the underlying cause of this disease, but immunomodulatory therapy should be considered in some selected cases.

Effects of environmental pollutants on airways, allergic inflammation, and the immune response.

Particulate and gaseous air pollutants are capable of damaging the airway epithelial lining and of shifting the local immune balance, thereby facilitating the induction of persistent inflammation. Epidemiological studies are inconclusive regarding whether air pollution increases the incidence of asthma and chronic bronchitis in the population. Clearly, environmental pollution can, however, precipitate attacks and emergency-room admissions in those already suffering from such conditions. The catastrophic potential of airborne pollution was demonstrated in the 1960s and 1970s, when inverted atmospheric pressure conditions trapped smog over cities on the Eastern coast of the United States and over Europe. This smog resulted in thousands of hospital admissions and dozens of deaths. With the general rise in the incidence of atopy and asthma in the Western population, it is of major public health interest to reduce, as much as possible, the exposure of such populations to anthropogenic and natural sources of pollution.

Noma in a full-term neonate.

Noma is an uncommon gangrenous process usually affecting malnourished children. A full-term neonate with orofacial noma, bilateral choanal atresia, and transient neutropenia with B cell deficiency is reported. This unusual appearance of noma in a well-nourished newborn might be related to the combination of choanal atresia and transient immune deficiency.

[Diagnosis of drug hypersensitivity--state of the art].

Adverse drug reactions are ubiquitous in outpatient as well as inpatient clinical care. An allergic drug reaction is an immunologically mediated adverse drug reaction that exhibits specificity and recurrence on re-exposure to the offending drug. The diagnosis and treatment of drug allergies is limited by a number of factors. In most instances the exact epitope causing the reaction is unknown, the immunological mechanism is unclear, the presence of immunological recognition is not predictive of a clinical reaction and the gold standard for diagnosis, the drug challenge, a complicated and sometimes dangerous endeavor. Nevertheless, during the past few years a serious attempt at standardization and validation of in vitro and in vivo techniques for the diagnosis of drug allergies, has been in progress. New methods, like the basophil surface marker for activation, CD63 are replacing old ones like histamine release for immediate type hypersensitivity reactions. For instance, in the field of beta-lactam hypersensitivity, the specific epitopes are better defined and standardized protocols for both immediate and delayed type reactions are in the process of being introduced. A standardized European Network of Drug Allergies (ENDA) questioner, published in 1999, permits systematic data gathering of events surrounding the acute drug reaction, facilitating later immunological investigation and diagnosis. This review attempts to summarize the present and some of the future options in the diagnosis of this common iatrogenic complication.