Our findings have emphasized that two amino acids substitution in Esc(1–21) with the corresponding d-enantiomers can reduce the peptide’s cytotoxicity and withstand the feasibility of using the diasteremer to alleviate pneumonia severity. Furthermore, we have also shown that in addition to having a therapeutic outcome, the diastereomer does not induce any undesirable side effect at the lung, but it is able to abate the inflammatory response upon bacterial infection, as corroborated by the results of immune cell differential counts, gene expression and lung histology analysis.