transforming-growth-factor-beta and Mastitis

Subclinical mastitis, as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine, interleukin-8 (IL8), was found to be common among breast feeding women in Bangladesh and Tanzania. Subclinical mastitis results in leakage of plasma constituents into milk, active recruitment of leukocytes into milk, and possible infant gut damage from inflammatory cytokines. Therefore, we wished to investigate whether subclinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission, that is, high milk viral load or increased infant gut permeability. HIV-infected South African women were recruited at the antenatal clinic of McCord's Hospital, Durban. Risks and benefits of different feeding strategies were explained to them and, if they chose to breast feed, they were encouraged to do so exclusively. Women and infants returned to the clinic at 1, 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern, a lactulose/mannitol test of infant gut permeability, and milk sample collection from each breast separately for analysis of Na/K ratio, IL8 concentration and viral load in the cell-free aqueous phase. Only preliminary cross-sectional analyses from an incomplete database are available at this point. Moderately (0.6-1.0) or greatly (>1.0) raised Na/K ratio was common and was often unilateral, although as a group right and left breasts did not differ. Considering both breasts together, normal, moderately raised or greatly raised Na/K was found, respectively, in 51%, 28%, 21% of milk samples at 1 week (n=190); 69%, 20%, 11% at 6 weeks (n=167); and 72%, 16%, 12% at 14 weeks (n=122). IL8 concentration significantly correlated with both Na/K and viral load at all times. Na/K correlated with viral load at 1 and 14, but not 6 weeks. At 1 and 14 weeks, geometric mean viral loads in samples with Na/K > 1.0 were approximately 4 times those in samples with Na/K < 0.6. At 1 week but not later times, exclusive breast feeding was associated with lower milk viral load than was mixed feeding. Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infant's diet. The results suggest that subclinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load. The importance of

Topics: Africa South of the Sahara; Breast Feeding; Cross-Sectional Studies; Female; HIV Infections; Humans; Infant; Infant Food; Infant, Newborn; Infectious Disease Transmission, Vertical; Interleukin-8; Intestinal Mucosa; Leukocytes; Mastitis; Milk, Human; Potassium; Risk Factors; Sodium; Transforming Growth Factor beta; Viral Load; Virus Shedding

Previously, we have found that subclinical breast inflammation, as indicated by raised breastmilk concentrations of sodium and the inflammatory cytokine, interleukin-8 (IL-8), was highly prevalent in Bangladesh and associated with poor infant growth. In order to investigate further the prevalence of subclinical breast inflammation and to assess the impact of dietary intervention, we studied rural Tanzanian women taking part in a study of dietary sunflower or red palm oil supplementation during late pregnancy and lactation. We measured breastmilk concentrations of IL-8, the anti-inflammatory cytokine, transforming growth factor-beta2 (TGF-beta) and the ratio of sodium to potassium. We also estimated systemic inflammation by plasma concentrations of the acute phase proteins, alpha1-acid glycoprotein and C-reactive protein. There were highly significant intercorrelations among milk Na/K ratio and concentrations of IL-8 and TGF-beta, the last only after treatment with bile salts which also improved TGF-beta recovery in the enzyme-linked immunosorbent assay (ELISA). Plasma acute phase protein concentrations tended to correlate with milk Na/K ratio and IL-8, suggesting that subclinical breast inflammation was related to systemic inflammation. Dietary supplementation with vitamin E-rich sunflower oil but not provitamin A-containing red palm oil decreased milk Na/K, IL-8 and TGF-beta at 3 months postpartum; however, the effect was significant only for Na/K ratio. The results suggest that milk Na/K ratio, IL-8, and TGF-beta all measure the same phenomenon of subclinical breast inflammation but that Na/K ratio, having the lowest assay variability, is the most useful. Subclinical breast inflammation may result in part from systemic inflammation and may be improved by increased dietary intake of vitamin E-rich sunflower oil.

Topics: Acute-Phase Proteins; Animals; Biomarkers; Developing Countries; Female; Helianthus; Humans; Interleukin-8; Mastitis; Milk; Plant Oils; Postnatal Care; Potassium; Pregnancy; Prenatal Care; Rural Health; Sodium; Transforming Growth Factor beta

To investigate the association of nonpuerperal mastitis with cytokines related to the helper T cells TH1/TH2 and TH17/Treg and associated immune balance.. From 2016 to 2021, we included 40 patients with non-puerperal mastitis who underwent surgery at China-Japan Friendship Hospital and compared them with 40 control patients with benign non-infectious breast disease. Hematoxylin-eosin staining detects inflammatory infiltrates of breast tissue. The expression of interferon γ and interleukin 4 in breast tissue was detected by immunofluorescence imaging, and the relative protein expression of TH1/TH2 and TH17/Treg cell-associated cytokines in CD4+ T cells was detected by western blotting. CD4+ T cells were isolated by fluorescence-activated cell sorting for detection of the relative protein expression of interferon γ and interleukin 4 in CD4+ T cells.. Hematoxylin-eosin staining showed that the nonpuerperal mastitis group had significantly greater inflammatory infiltration than the control group. Immunofluorescence images showed the relative fluorescence intensity of interferon γ was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative fluorescence intensity of interleukin 4 did not significantly differ between the 2 groups (P = .0686). Western blotting revealed that the relative protein expression of interferon γ, interleukin 2, and interleukin 17 was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative protein expression of interleukin 4 (P = .0512), interleukin 10 (P = .3088), and transforming growth factor β (P = .0653) did not significantly differ between the 2 groups. Flow cytometry of isolated CD4+ T cells showed the relative protein expression of interferon γ was significantly higher in the nonpuerperal mastitis group than in the control group (P < .001), but the relative protein expression of interleukin 4 did not significantly differ between the 2 groups (P = .0680).. The expression of the TH1 cytokines interferon γ and interleukin 2 and the TH17 cytokine interleukin 17 was significantly higher in patients with nonpuerperal mastitis, while the TH2 cytokine interleukin 4 and the Treg cytokines interleukin 10 and transforming growth factor β were expressed at lower levels. This study provides new research ideas for the treatment of mastitis.

Topics: Cytokines; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Interferon-gamma; Interleukin-10; Interleukin-17; Interleukin-2; Interleukin-4; Mastitis; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Th2 Cells; Transforming Growth Factor beta

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cadherins; Carboplatin; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Clinical Trials as Topic; Diagnosis, Differential; Docetaxel; Drug Resistance, Neoplasm; Female; Humans; Inflammatory Breast Neoplasms; Lapatinib; Mastitis; Molecular Targeted Therapy; Neoadjuvant Therapy; Neoplasm Staging; Neoplastic Cells, Circulating; Quinazolines; Receptor, ErbB-2; Remission Induction; Taxoids; Transforming Growth Factor beta; Trastuzumab; Treatment Outcome