Oral administration of muramyl dipeptide into mice modulates cell proliferation, immunoglobulin synthesis and cytokine mRNA levels in gut associated lymphoid tissues.
Muramyl peptides (MDPs) are synthetic immunostimulants capable of potentiating a multitude of immune functions following parenteral administration into a host. The parent molecule MDP was also found to exert certain activities when applied via the oral route. Thus, we have studied the effect of oral treatment of mice with MDP on the lymphoproliferative responses, immunoglobulin secretion and cytokine induction in gut-associated lymphoid tissues (GALT) employing lymphocyte transformation test, ELISA and RT-PCR, respectively. Cells derived from Peyer's patches (PP) of mice orally primed with MDP were found to have enhanced proliferative responses to different mitogens and to secrete significantly more IgG, IgM and IgA immunoglobulins than cells from unprimed mice. These effects were not observed with cells derived from mesenteric lymph nodes (MLN) or spleens of MDP-primed mice. However, oral administration of MDP resulted in the up-regulation of interleukin-6 (IL-6) mRNA in MLN and down-regulation of IL-4 and tumour necrosis factor-alpha (TNF-alpha) mRNAs in MLN, spleens and PP. These studies suggest that selective modulations of GALT responses by orally administered MDP are achievable and imply that these agents may be useful in the therapy and prophylaxis of allergic diseases.
Zunić
M
M
Sandoz Research Institute, Vienna, Austria.
Kricek
F
F
Dukor
P
P
Bahr
G M
GM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics; D005260:Female; D007136:Immunoglobulins / Q000096:biosynthesis*; D008221:Lymphoid Tissue / Q000737:chemistry*; D008643:Mesentery; D051379:Mice; D010581:Peyer's Patches; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry
D016207:Cytokines; D007136:Immunoglobulins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine