Oral Feeding of Cow Milk Containing A1 Variant of β Casein Induces Pulmonary Inflammation in Male Balb/c Mice

Sci Rep. 2020 May 15;10(1):8053. doi: 10.1038/s41598-020-64997-z.


Milk is globally consumed as a rich source of protein and calcium. A major protein component of milk is casein, with β-casein having 2 major variants A1 and A2. Of these, A1 casein variant has been implicated as a potential etiological factor in several pathologies, but direct effect on lungs has not been studied. The objective of the present study was to evaluate the A1and A2 β casein variants of cow milk as factors causing allergic airway disease in murine model. Mice fed with A1A1 milk exhibited increased airway hyperresponsiveness with increasing concentration of bronchoconstrictor (methacholine), which was not observed in mice fed with A2A2 milk. Significantly elevated levels of IL-4 and IL-5 were found in bronchoalveolar lavage and serum of A1A1 variant fed mice. Increased IgE and IgG levels along with increased infiltration of lymphocytes and eosinophils, leading to peribronchial inflammation was also observed in A1A1 variant fed mice, although, no goblet cell hyperplasia or airway remodeling was observed. In contrast, A2A2 milk fed mice presented phenotype matching the control group, while A1A2 milk fed group presented an intermediate phenotype. In summary, our results show that A1 form of cow milk has a proinflammatory effect on the lung resulting in phenotype closely matching with the typical allergic asthma phenotype.

MeSH terms

  • Animal Feed / adverse effects*
  • Animals
  • Biomarkers
  • Caseins / adverse effects*
  • Caseins / genetics*
  • Cattle
  • Cytokines / metabolism
  • Disease Susceptibility*
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Genetic Variation*
  • Genotype
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Milk / adverse effects*
  • Pneumonia / etiology*
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism


  • Biomarkers
  • Caseins
  • Cytokines
  • Immunoglobulin G
  • Inflammation Mediators
  • Immunoglobulin E