ABSTRACT
The injection of alpha-MSH or of one of its analogues ([Nle4-D.Phe7] alpha-MSH4-10) reduced, in vivo, the release of two cytokines (IL-1 alpha and TNF alpha) involved in inflammation. The inflammatory state was induced in BALB/c mice by intraperitoneal injection of a sublethal dose of lipopolysaccharides (LPS). The assay of these cytokines by ELISA showed a reduction of 20% with alpha-MSH and between 30 and 60% with the alpha-MSH analogue. The alpha-MSH or the analogue was administered in one of two ways: intravenously or subcutaneously. The most efficient method seemed to be the subcutaneous one because it improved the activity 10,000 times more than the intravenous method. Moreover, the analogue induced a regression of mortality in the animals treated by the intravenous method. Our results show that alpha-MSH and one of its analogues inhibit IL-1 alpha and TNF alpha, and can be used as anti-inflammatory molecules.
Subject(s)
Interleukin-1/blood , Lipopolysaccharides/pharmacology , Tumor Necrosis Factor-alpha/pharmacology , alpha-MSH/analogs & derivatives , Animals , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Injections, Intravenous , Injections, Subcutaneous , Mice , Mice, Inbred BALB C , alpha-MSH/pharmacologyABSTRACT
In this preliminary report, we describe our inability to induce IgE antibody to a well-characterized bacterial component, the membrane proteoglycan of Klebsiella pneumoniae and its major protein fraction FIII-B in BALB/c mice. In contrast, an immunomodulatory effect of membrane proteoglycan of K. pneumoniae on the IgE and IgG antibody responses to ovalbumin could be demonstrated.
Subject(s)
Immunoglobulin E/immunology , Klebsiella pneumoniae/immunology , Proteoglycans/immunology , Allergens/immunology , Animals , Female , Immunoglobulin G/immunology , Mice , Mice, Inbred BALB C , Ovalbumin/immunologyABSTRACT
Ribosomal preparations from Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae were investigated with respect to their activating capacity towards murine lymphoid cells. The proliferation of BALB/c spleen cells was induced in a dose-dependent fashion (from 1 to 100 micrograms/ml) by ribosomes of K. pneumoniae, H. influenzae, and S. pyogenes with a peak activity at 48 or 72 hr of culture. The majority of the blast cells induced by these ribosomal preparations were positive for surface-immunoglobulin (S-Ig) and negative for Thy 1.2. Furthermore, K. pneumoniae, H. influenzae, and S. pyogenes ribosomes induced the synthesis of IgM and some IgA. Cell proliferation and induction of IgM production were also demonstrated with the 3 ribosomal preparations using spleen cells from athymic nude (nu+/nu+) mice, Lyb-5-defective CBA/N spleen cells, B cell-enriched and T cell-depleted BALB/c spleen cell suspensions, as well as spleen cells from the Ips gene-deficient C3H/HeJ strain. Cell culture supernatants contained specific anti-ribosome IgM antibodies. Antibodies of other specificities (anti-sheep erythrocytes) were also demonstrated in supernatants from K. pneumoniae-stimulated cultures. Evidence against a possible role of contamination of K. pneumoniae and H. influenzae ribosomes by lipopolysaccharide- or lipid A-associated proteins in this effect is discussed. Ribosomes from S. pneumoniae did not induce 3H-thymidine incorporation nor Ig production. None of the 4 ribosomal preparations was found to stimulate T cell blastogenesis or to induce interleukin-2 production by naive BALB/c spleen cells. Finally, ribosomes from H. influenzae, S. pyogenes, S. pneumoniae but not those of K. pneumoniae stimulated interleukin-1 production by adherent spleen cells, from BALB/c mice.
Subject(s)
B-Lymphocytes/physiology , Immunoglobulins/biosynthesis , Ribosomes/immunology , Animals , Antigens, Bacterial/immunology , B-Lymphocytes/immunology , Cells, Cultured , Female , Interleukin-1/biosynthesis , Lymphocyte Activation , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred CBA , Mice, Nude , Ribosomes/ultrastructure , Spleen/cytology , Spleen/metabolismABSTRACT
Nonspecific protection against infectious aerosols of influenza A virus was obtained in Swiss mice after vaccination by aerosols of bacterial ribosomes together with membranal glycoproteins extracted from Klebsiella pneumoniae as the adjuvant. It was shown that repeated stimulant aerosols were necessary to obtain this protection. Routine estimation of serum interferon levels after administration of the association of ribosomes plus membranal glycoproteins to the animals by aerosol or intravenous route showed that there was no correlation between protection and the presence of serum interferon. It was shown that the serum interferon-inducer activity was due to ribosomes. No induction of serum interferon was obtained with membranal glycoproteins used separately. Local liberation of interferon in the mucous membrane of the upper respiratory tract was not investigated.
Subject(s)
Adjuvants, Immunologic , Bacterial Proteins/immunology , Glycoproteins/immunology , Interferons/blood , Klebsiella pneumoniae/immunology , Membrane Proteins/immunology , Orthomyxoviridae Infections/prevention & control , Ribosomes/immunology , Adjuvants, Immunologic/administration & dosage , Aerosols , Animals , Bacterial Vaccines/administration & dosage , Female , Haemophilus influenzae/immunology , Influenza A virus , Injections, Intravenous , Mice , Streptococcus pyogenes/immunologySubject(s)
Immunoglobulin A, Secretory/analysis , Immunoglobulin A/analysis , Respiratory System/immunology , Antibody Formation , Asthma/immunology , Bronchiectasis/etiology , Female , Humans , IgA Deficiency , Immunization , Immunoglobulin G/analysis , Male , Respiratory System/physiopathology , Respiratory Tract Infections/immunology , Specimen Handling , Sputum/immunologySubject(s)
Adjuvants, Immunologic , Bacterial Infections/prevention & control , Bacterial Vaccines , Immunoglobulin A , Immunoglobulin G , Respiratory Tract Infections/prevention & control , Vaccination , Adjuvants, Immunologic/administration & dosage , Adolescent , Asthma/therapy , Bacterial Vaccines/administration & dosage , Bronchiectasis/therapy , Bronchitis/therapy , Child , Clinical Trials as Topic , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Injections, Subcutaneous , Sputum/immunology , Time FactorsABSTRACT
The current possibility of measuring at one and the same time serum IgA and sputum SIgA, has led to precision in knowledge of IgA deficits in respiratory pathology. The authors report 21 cases detected in a group of 1000 patients (adults, adolescents and children), suffering from various chronic respiratory disorders and who had either total deficits in serum and sputum IgA (6 cases) or partial deficits (15 cases - mixed [5], serum IgA [5i1, sputum IgA [5]. In 9 cases the assoicated respiratory disorder was bronchiectasis, in 7 recurrent rhino-tracheo-bronchitis and in 5 asthma. In no cases were any extra-respiratory manifestations noted, in particular digestive disturbance or auto-immune disease. In some cases there was an associated deficit in IgE and, much less commonly, in IgG or M. Cellular immunity was not altered. The authors then discuss the place of IgA and SIgA deficitis in the pathogenesis of chronic respiratory pathology as well as their substitutive treatment using natural human immunoglobulins and the results thereof.