The Open Allergy Journal

2012, 5 : 53-61
Published online 2012 August 24. DOI: 10.2174/1874838401205010053
Publisher ID: TOALLJ-5-53

Suppression of PAMPs, Pathogen-Associated Microbial Patterns, Induced Cytokine Synthesis of PBMC, Human Blood Mononuclear Cells, by Immunoglobulin Preparation

Ayumi Yamamoto , Noriko N. Miura , Toshiaki Oharaseki , Kei Takahashi , Shiro Naoe , Kazuo Suzuki and Naohito Ohno
Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192- 0392, Japan.

ABSTRACT

The applications of immunoglobulin preparation for intravenous injection (IVIg) for various intractable diseases are increasing. The two major clinical indications for IVIg are the replacement therapy and the anti-inflammation therapy for a variety of acute and chronic autoimmune diseases. One of the proposed mechanisms of IVIg activity is the modulation of cytokine expression and function; therefore, we analyzed the effect of IVIg on pathogen-associated molecular pattern (PAMP)-induced cytokine production by peripheral blood mononuclear cells (PBMCs). The production of tumor necrosis factor-α (TNF-α) as a result of stimulation with lipopolysaccharide (LPS), polyinosinic-polycytidylic acid sodium salt (Poly I:C), or Pam3CysSerLys4 (Pam3) was significantly inhibited by sulfonated-IVIg (S-IVIg), or by F(ab')2. Assessed by one-color microarray analysis, the expressions of 229 genes were inhibited to 1/200 or less by F(ab')2. On the other hand, the expressions of 159 genes were increased by more than 100-fold by F(ab')2. According to these results, it was suggested that IVIg inhibits inflammatory PAMPs-induced cytokine production by PBMCs, due to the modulation of varieties of gene expression.

Keywords:

anti-inflammatory effect, intravenous immunoglobulin (IVIg) therapy, microarray analysis, pathogen-associated microbial patterns (PAMPs).