Skin-window-induced inflammation in breast cancer patients: a study of macrophage migration.

A decreased number of macrophages has previously been demonstrated by means of skin-window assays in operable breast cancer patients. However, in this type of cellular inflammatory response, a varying intensity of cellular activation, cellular recruitment and macrophage chemotaxis exists. In this study, we performed skin windows after stimulation by a chemo-attractant (FMLP) and a recall antigen (Candidin-latex). Cellular responses were classified in 19 breast cancer patients according to the presence (A+) or absence (A0) of macrophage activation by comparison to healthy controls. In 13 A0 patients, the admixture of a cytokine (IFN alpha) and an immunomodulator (P40) to one agent or the other or both resulted in the restoration of macrophage functions. Our study shows that uniform cellular responses to chemo-attractants and antigens are observed in healthy and not immunocompromised individuals as assessed by skin-window tests. However, the cellular response recorded in immunodeficient cancer patients is altered. It also shows that the admixture to chemoattractants and antigens of particular cytokines or better still of an immunomodulator displaying a wide spectrum of activity offers a way of restoring macrophage functions. Individual responses to immunotherapy in clinical oncology may be related to such results.

Does reversed-type anaphylaxis in healthy subjects mimic a real allergic reaction?

Immediate and late cutaneous reactions were induced in healthy and atopic subjects by anti-IgE challenge and a skin-window technique was used in order to verify if the pattern of cells observed at 24 hr was similar in both groups. The study was first performed under basal conditions, and in a second double-blind cross-over step, it was performed again during treatment with cetirizine 10 mg b.i.d. and terfenadine 60 mg b.i.d. Anti-IgE challenge was followed by a significant eosinophil accumulation in atopic subjects only. Cetirizine significantly inhibited this phenomenon while terfenadine showed a mild non-significant inhibitory effect.

Reactivity of human basophils to anti-IgE and protein A in atopic dermatitis.

We compared by basophil degranulation and histamine release the reactivity to protein A and anti-IgE of the basophils from 3 groups of patients: group I (blood donors), group II (rhinitis) and group III (atopic dermatitis). We demonstrated that histamine release and basophil degranulation gave tightly correlated results and that by both methods group III was significantly (p less than 0.01) more sensitive to the effectors than the two other groups. Protein A and anti-IgE stimulation curves showed a rebound effect at low concentrations of effectors. This was, however, only significant (p less than 0.01) for group III. Bacterial hypersensitivity may be IgE-mediated and may be related to the increased sensitivity to bacterial antigens and the severity of atopic dermatitis in patients infected by Staphylococcus aureus.

[Questions raised by the clinical and biological polymorphism of atopic dermatitis]. / Questions posées par le polymorphisme clinique et biologique de la D.A.

AD is not clearly located amongst the diseases of allergy, but it has some common features with respiratory tract allergy. 1. The disregulation of IgE and also T cell abnormalities. 2. Long-lasting inflammatory flare-up of AD resembles more delayed-type mechanisms of hypersensitivity than the precocious immediate type of respiratory allergy. Furthermore, the accumulation of inflammatory cells (PMN and monocytes-macrophages) in the sites involved in AD have not yet been thoroughly investigated. 3. Another feature of AD is its frequent association with respiratory tract allergy, though the immediate type reactions observed with respiratory symptoms are not necessarily linked by common mechanisms to AD cutaneous lesions. 4. Cutaneous lesions that suggest AD are often seen in disorders where there are genetic abnormalities, though in spite of a common eczematous aspect, the etiology and prognosis are entirely different from AD.

Skin eosinophilia in atopic patients.

The responses of six atopic and six control patients to the intracutaneous administration of platelet-activating factor (PAF) acether, of the leukocyte secretagogue and chemoattractant f-methionyl-leucyl-phenylalanine (FMLP), and of allergens were studied. Immediate wheal-and-flare skin reactions to allergens and to PAF acether in atopic patients were the same, and when reactions were compared to reactions of nonatopic patients, these reactions to PAF acether and to FMLP were of equivalent intensity. Late-phase reactions were not observed macroscopically with allergen, PAF acether, or FMLP. The cellular responses, assessed by the Rebuck skin window technique, demonstrated a late (24 hours) eosinophilic response to the allergen and to both inflammatory agents, with 33% to 44% of intensively degranulated eosinophils. In comparison, very few, if there were any, eosinophils were observed in the nonatopic patients. Most infiltrated cells were neutrophils. The accumulation of eosinophils in atopic human skin indicates a potent eosinophilotactic activity restricted to the allergic patients. A similar cellular reaction has been observed in lungs from guinea pigs injected with PAF acether or with allergen, and in patients with severe asthma. The chemoattractant activity of FMLP toward eosinophils cannot be accounted for by its histamine-releasing activity and remains to be explained.

Inhibitory effect of cetirizine 2HCl on eosinophil migration in vivo.

The effect of a potent antihistamine, cetirizine, was studied on allergic patients and normal subjects by means of an in-vivo 'skin window' technique. All subjects showed significant inhibition of skin-test responses to grass pollen, compound 48/80, histamine and methacholine, after administration of a single dose (10 mg) of cetirizine. Compared to placebo, cetirizine significantly decreased the eosinophils attraction at skin sites challenged with grass pollen and compound 48/80. In allergic patients no change in eosinophil migration pattern was noted with histamine and methacholine skin-tested sites. In normal subjects, compound 48/80 and histamine did not induce eosinophil accumulation and cetirizine did not modify cellular patterns as compared to placebo. These results suggest that cetirizine acts on eosinophil migration by inhibiting the release of mast cell mediators or inhibiting the eosinophilotactic mediators themselves.

[Microbial allergy and immunotherapy in allergologic practice]. / Allergie microbienne et immunothérapie en pratique allergologique.

Microorganisms (viruses, bacteria, fungi) may play a prominent role in triggering allergic manifestations. Either indirectly by releasing potentiating or immuno-modulation factors such as L.P.S. and peptidoglycans, or more directly by their numerous histamine--releasing potentials. However a difficulty remains to establish the relevance of such inter-relationships. The near future will probably give rise to better defined components from microbial origin, with a higher degree of specificity.

Preliminary experimental and clinical results with inactivated allergens conjugated to the Corynebacterium granulosum-derived immunomodulator P40.

Allergoids have been used successfully for immunotherapy of allergic disorders. It has appeared to us that the effect of allergoids could be potentiated by their coupling to an immunomodulator. In the present study we show that a conjugate made up of the coupling of ovalbumin through glutaraldehyde action to the C. granulosum-derived immunomodulator P40 is completely devoid of antigenicity and of cross-reactivity with ovalbumin. This conjugate was found to significantly inhibit mast cell degranulation. It also proved to be capable of protecting against the lethal systemic anaphylactic shock sensitized mice. Immunotherapy was performed in patients hypersensitive to either the pollen of Dactylis glomerata or to the house dustmite allergens using the conjugates made of the specific allergens and of the P40. Clinical improvement was observed in a significant percentage of the patients subjected to immunotherapy. Administration of the conjugates did not result in untoward reactions in any of the patients.

Calcium phosphate adjuvanted allergens.

Calcium phosphate has been used for many years as an adjuvant for vaccines. Results of field trials using calcium phosphate in several countries have been published and demonstrate high immunogenicity and the absence of untoward reactions. This paper presents preliminary results of studies on the use of calcium phosphate, instead of aluminum compounds, for preparing adsorbed allergens. These were performed with purified house dust, mite, and grass pollen extracts. Immunotherapy with house dust and mite extracts gave a high rate (70%) of satisfactory therapeutic results. Efficacy was compared with immunization carried out with fluid preparations under the same conditions. It was found that satisfactory results were of the same order, but elicited a higher number of injections. Immunotherapy with calcium phosphate adjuvanted allergens was also equal, as with aluminium adjuvanted allergens, according to published data. Good tolerance was noted for adsorbed grass pollen extracts, but clinical evaluation of results can only be reported after treatments during at least three seasons.

Immunochemical study of the venom from the hornet Vespa orientalis (hymenoptera:Vespinae).

Venom from young (0 to 48 hours after eclosion) Vespa orientalis should presumably be less allergenic and/or antigenic than venom from adult hornets. This point was confirmed by skin tests, by crossed immunoelectrophoresis and by radioallergosorbent test (RAST), using rabbit IgG antibodies and human IgE antibodies. It is suggested that the venom of young hornets could have therapeutic applications.

[Treatment of recurrent urogenital infections by immunomodulation]. / Traitement des infections urogénitales récidivantes par immunomodulation.

In recurrent urogenital infections in which no curable cause can be found, long term antibiotic therapy is often the only possible form of treatment. After performing appropriate skin tests, the authors evaluated the effectiveness of vaccination consisting of antigen therapy and an immunostimulant, P 40, in 20 patients. The recurrent infections were controlled in the cases in which this combination was used; in half of the cases, maintenance vaccination was required for a period of 2 or 3 years.

Treatment of relapsing chronic infections of the respiratory tract. A comparative study of the effectiveness of non specific immunotherapy with the immunoadjuvant P40 and of vaccinotherapy.

O tratamento de infeccoes cronicas recidivantes (I.C.R.) encontra muitas dificuldades. No presente estudo, o uso do imunoadjuvante P40, quer isolado, quer associado a vacinoterapia no tratamento de I.C.R., demonstrou ser muito eficaz, ao passo que a vacinoterapia isoladamente nao o foi.Foi aventada a hipotese de que a imunidade mediada por celulas pode desempenhar papel importante no controle das I.C.R., uma vez que a melhora clinica dos pacientes foi acompanhada de positivacao de testes cutaneos anteriormente negativos, testes estes realizados quer com o agente infeccioso especifico, quer com antigeno inespecifico de reforco