Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12- IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centres to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised.
Adjuvants, Immunologic ; adverse effects ; therapeutic use ; BCG Vaccine ; adverse effects ; immunology ; therapeutic use ; Humans ; Immunologic Deficiency Syndromes ; diagnosis ; immunology ; Infant, Newborn ; Mycobacterium Infections ; prevention & control ; Mycobacterium bovis ; drug effects ; Neonatal Screening ; methods ; Risk Assessment ; Vaccination ; adverse effects ; methods

OBJECTIVETo study the protective effect of atractylenolide I on immunological liver injury induced by BCG and LPS.

METHODKunming mice were randomly divided into 6 groups: the normal group, the model group, positive control biphenyl group, the atractylenolide I high does group, the atractylenolide I middle dose group and the atractylenolide I low dose group (60, 120, 240 mg x kg(-1)), with 12 mice in each group. Immunological liver injury in mice was induced by BCG and LPS to compared liver index and spleen index and detect content of serum ALT, AST, MDA and GSH-px in serum and NO, iNOS, TNF-alpha in serum and liver homogenate. Liver pathological changes were observed by HE staining.

RESULTBoth of atractylenolide I and biphenyl remarkably decrease the increased live index and spleen index (P < 0.05), improve the histopathological changes in liver and pathological grades of liver tissues and relieve the inflammatory reaction induced by BCG and LPS. They showed a notable effect in improving MDA and GSH-px in serum.

CONCLUSIONAtractylenolide I can obviously protect immunological injury liver a dose-dependent manner within the range of test doses. Its mechanism may be related to release or over expression of inhibitory inflammatory medium such as NO, iNOS and TNF-alpha.

Animals ; Chemical and Drug Induced Liver Injury ; immunology ; metabolism ; pathology ; prevention & control ; Lactones ; pharmacology ; Lipopolysaccharides ; adverse effects ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice ; Mycobacterium bovis ; immunology ; Oxidative Stress ; drug effects ; immunology ; Sesquiterpenes ; pharmacology

OBJECTIVETo study the effect of bacillus Callmette-Guérin (BCG) on cytotxicity of cytotoxic T lymphocyte (CTL) from human peripheral blood of children with acute lymphoblastic leukemia (ALL) for killing HL-60 cells in vitro.

METHODSThe mononuclear cells were isolated from peripheral blood of ALL children and healthy children, and were cultured with RPMI1640, interleukin-2 (IL-2), phytohemagglutinin (PHA) and BCG.The growth of CTLs was observed by light microscopy. The proportions of CD3, CD3+CD4+ and CD3+CD8+ were determined by flow cytometry 10 days after culture. MTT method was performed to detect the cytotoxicity of CTLs for killing HL-60 cells.

RESULTSNeither the cell number nor the volume of CTLs changed significantly within 2 days of culture, but both began increasing on the 3rd day of culture and reached a peak on the 6-10th days. On the 10th day of culture, the cell number of CTLs in the BCG treatment group was much higher than in the group without BCG treatment. The CD3+CD8+ proportion in the leukemia group was much higher than in the control group. With the effect of BCG, the CD3+CD8+ proportion of the two groups became much higher. The cytotoxicity of CTLs for killing HL-60 cells in the leukemia group was weaker than in the control group.

CONCLUSIONSBCG along with IL-2 and PHA promotes the proliferation of CTLs and enhances the ability of CTLs in killing HL-60 cells.

Child, Preschool ; Cytotoxicity, Immunologic ; Female ; HL-60 Cells ; Humans ; Interleukin-2 ; pharmacology ; Lymphocyte Activation ; Male ; Mycobacterium bovis ; immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; T-Lymphocytes, Cytotoxic ; immunology

This study was purposed to investigate the effect of bacillus calmette-guerin (BCG) on the expansion of human dendritic cells (DC) from peripheral blood of pediatric patients with leukemia in vitro. The experiment was divi-ded into two groups: the control and the test group, and the latter group was divided into 3 subgroups: BCG (only BCG), GTI (GM-CSF, TNF-α, IL-4) and GTIB (GM-CSF, TNF-α, IL-4 plus BCG). On day 9 of culture the DCs were counted in each groups, the phenotypes of DC were determined by flow cytometry and these DC were stained with Wright-Giemsa for observation and photography under microscopy. The results showed that the test groups all obtained a certain amount of typical DC; the number of DC in the BCG subgroup is lower than that in the GTI and GTIB subgroups (t=4.20; 6.36, p<0.01); there was no significant difference between the GTI and the GTIB subgroups (t=2.25; p>0.05). The rate of CD1a+ in the BCG subgroup was obviously higher than that in the control group (t=3.04, p<0.05), but was lower than that in the GTI and the GTIB subgroups (t=2.79, 6.41, p<0.05), there was no significant difference between the GTI and the GTIB subgroups (t=0.65, p>0.05). The rate of HLA-DR+, CD83+ in the BCG group was higher than that in the control group (t=4.77, 4.15; p<0.05), but lower than that in the GTI and the GTIB subgroups (t=6.65, 3.19; p<0.05). The rate of HLA-DR+, CD83+ in the GTI subgroup was lower than that in the GTIB subgroup (t=5.64, 2.98; p<0.05). It is concluded that BCG not only promotes the proliferation of DC derived from human peripheral blood of leukemia patients in vitro, but also cooperates with rhGM-CSF, rhTNF-α and rhIL-4 in promoting the maturation of DCs.
BCG Vaccine ; immunology ; pharmacology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Child ; Dendritic Cells ; cytology ; drug effects ; Humans ; Leukemia ; immunology ; Mycobacterium bovis ; immunology

Adjuvants, Immunologic ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin G ; blood ; Male ; Mycobacterium bovis ; immunology ; Nephrotic Syndrome ; immunology ; prevention & control ; Nucleic Acids ; therapeutic use ; Polysaccharides, Bacterial ; therapeutic use ; Recurrence

OBJECTIVETo explore the clinical manifestation, immune abnormality and outcome of disseminated Bacille Calmette-Guérin (BCG) infection in children.

METHODThe clinical data of 18 children with disseminated BCG infection seen from January 2000 to December 2007 were analyzed retrospectively.

RESULTThirteen of the children were male among 18 patients. Disseminated infection first appeared in armpit lymph nodes ipsilateral to the vaccination site, then spread to lungs in 15, lymphnodes of mediastinum or abdominal cavity in 18, skin and soft tissues in 5, skeletons in 4, liver in 4, spleen in 8, kidney, adrenal gland or meninges in 3. Twelve children were diagnosed to have primary immunodeficiency; 3 had severe combined immunodeficiency (SCID); 7 had chronic granulomatous disease (CGD), 2 had IL-12/IFN-gamma passageway deficiency. Eleven of the 18 patients died, and the remaining 7 patients were followed up from 1 to 9 years and are alive at present, but presented recurrent skin and bone tuberculosis in 4 and recurrent other infection in 3.

CONCLUSIONMost Children with disseminated BCG infection had primary immunodeficiency. CGD and IL-12/IFN-gamma passageway deficiency accounted for considerable proportion, so special immune function should be detected in these patients. The prognosis was poor. The type of the immunodeficiency diseases should be identified in early stage and the specific immune treatment should be given to the patients.

BCG Vaccine ; adverse effects ; Child, Preschool ; Female ; Humans ; Immunologic Deficiency Syndromes ; etiology ; Infant ; Lymph Nodes ; Male ; Mycobacterium bovis ; pathogenicity ; Retrospective Studies ; Tuberculosis ; immunology ; microbiology ; pathology

Animals ; Asthma ; immunology ; BCG Vaccine ; immunology ; Humans ; Mycobacterium bovis ; immunology ; T-Lymphocyte Subsets ; immunology

To improve the efficacy of peptide P277 in preventing autoimmune diabetes, heat shock protein 65 kD (HSP65) of Mycobacterium tuberculosis var. bovis was fused with linear polypeptide epitope of P277 and expressed as soluble protein in Escherichia coli. The fusion protein HSP65-P277 was purified by anion exchange column chromatography and then used to immunize prediabetic NOD mice with three ip inoculations in absence of adjuvants. Serum samples from the immunized mice were collected monthly and the concentration of blood glucose was measured. The study showed that administration of HSP65-P277 to NOD mice could prevent the development of diabetes more efficiently than the peptide P277 itself or HSP65. Fused to heat shock protein 65 of Mycobacterium tuberculosis could improve the efficacy of diabetes prevention of P277 in nonobese diabetic mice. The results suggest the fusion protein of HSP65-P277 would be useful for treating insulin-dependent diabetes mellitus.
Animals ; Bacterial Proteins ; biosynthesis ; genetics ; immunology ; Chaperonin 60 ; Chaperonins ; biosynthesis ; genetics ; immunology ; Diabetes Mellitus, Type 1 ; prevention & control ; Escherichia coli ; genetics ; metabolism ; Female ; Heat-Shock Proteins ; genetics ; immunology ; Immunization ; Mice ; Mice, Inbred NOD ; Mycobacterium bovis ; Peptide Fragments ; biosynthesis ; genetics ; immunology ; Random Allocation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; Vaccines, Synthetic ; genetics ; immunology

OBJECTIVETo investigate the protective effects of Hongbeiyegen (HBYG) against immunological liver injury induced by bacille Calmette-Guerin (BCG) and lipopolysaccharide (LPS).

METHODSImmunological liver injury was induced in rats by BCG and LPS injected via the tail vein. The liver index, thymus index and spleen index were calculated and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) and liver homogenate contents of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined.

RESULTSHBYG significantly improved the liver index, thymus index and spleen index, and reduced the serum levels of ALT, AST and NO, and as the liver homogenate contents of TNF-alpha and IL-1beta.

CONCLUSIONHBYG offers obvious protective effects against immunological injury liver in mice.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Chemical and Drug Induced Liver Injury ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Euphorbiaceae ; chemistry ; Female ; Interleukin-1beta ; metabolism ; Lipopolysaccharides ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases ; immunology ; prevention & control ; Male ; Mice ; Mice, Inbred Strains ; Mycobacterium bovis ; Nitric Oxide ; blood ; Phytotherapy ; Plant Roots ; chemistry ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo observe the effect of polysaccharide ATPS-2 from Armillariella tabescens on the immunological liver injury in mice induced by BCG plus LPS.

METHODBCG and LPS were adopted to establish BCG plus LPS liver injury model in mice. The content of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NO, the activity of superoxide dismutase (SOD) and malondiadehyde (MDA) content of liver homogenate in mice were measured by colorimetric method. The content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), on serum were measured by enzyme linked immunosorbent assay (ELISA) , and T- and B-lymphocyte proliferation were measured by MTT. Index of liver, spleen and thymus were calculated after treatment.

RESULTPolysaccharide ATPS-2 from A. tabescens (25, 50, 100 mg x kg(-1)) could obviously reduce the high level of ALT, AST, NO and TNF-alpha, IL-1 on serum, inhibit the high level of MDA, increase the low activity of SOD in liver homogenate and enhance T-and B-lymphocyte proliferation, elevate the spleen, thymic index and decrease liver index of the mice to different extent.

CONCLUSIONPolysaccharide ATPS-2 from A. tabescens had apparently protective effects in the immunological liver injury mice induced by BCG plus LPS.

Agaricales ; chemistry ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; B-Lymphocytes ; cytology ; Cell Proliferation ; drug effects ; Chemical and Drug Induced Liver Injury ; Interleukin-1 ; blood ; Lipopolysaccharides ; Liver ; metabolism ; pathology ; Liver Diseases ; immunology ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mice ; Mycobacterium bovis ; Nitric Oxide ; blood ; Polysaccharides ; isolation & purification ; pharmacology ; Protective Agents ; isolation & purification ; pharmacology ; Random Allocation ; Superoxide Dismutase ; metabolism ; T-Lymphocytes ; cytology ; Tumor Necrosis Factor-alpha ; blood