After emigration from the bone marrow to the peripheral blood, monocytes enter tissues and differentiate into macrophages, the prototype scavenger of the immune system. By ingesting and killing microorganisms and removing cellular debris, macrophages also process antigens as a first step in mounting a specific immune response. IL-32 is a cytokine inducing proinflammatory cytokines and chemokines via p38-MAPK and NF-B. In the present study, we demonstrate that IL-32 induces differentiation of human blood monocytes as well as THP-1 leukemic cells into macrophage-like cells with functional phagocytic activity for live bacteria. Muramyl dipepide (MDP), the ligand for the intracellular nuclear oligomerization domain (NOD) 2 receptor, has no effect on differentiation alone but augments the monocyte-to-macrophage differentiation by IL-32. Unexpectedly, IL-32 reversed GM-CSF/IL-4-induced dendritic cell differentiation to macrophage-like cells. Whereas the induction of TNF␣, IL-1␤, and IL-6 by IL-32 is mediated by p38-MAPK, IL-32-induced monocyte-to-macrophage differentiation is mediated through nonapoptotic, caspase-3-dependent mechanisms. Thus, IL-32 not only contributes to host responses through the induction of proinflammatory cytokines but also directly affects specific immunity by differentiating monocytes into macrophage-like cells.immune cell differentiation ͉ inflammation ͉ muramyl dipeptide ͉ cytokine ͉ antigen presentation I n addition to their role for the activation of the antimicrobial function of leukocytes, cytokines have an important role for the proliferation and differentiation of myeloid cell populations. IL-32 is a proinflammatory cytokine that is induced by IL-18 and IFN-␥ in human epithelial cells (1). The gene expression of IL-32 is increased in human T lymphocytes and natural killer cells when stimulated by mitogens or IL-2 (2, 3). In turn, IL-32 also induces the synthesis of proinflammatory cytokines such as IL-1␤, IL-6, and TNF␣. Elevated levels of mRNA have been reported in synovial tissue explants from patients with rheumatoid arthritis, but not osteoarthritis (4). The intensity and frequency of tissue-staining levels of IL-32 protein in synovial cells of patients with rheumatoid arthritis correlate with disease activity, as well as tissue levels of TNF␣, IL-1␤, and IL-18 (5). Affected tissues from patients with Crohn's disease and ulcerative colitis show prominent staining for IL-32 (6, 7). IL-32 is produced by peripheral blood mononuclear cells (PBMCs) stimulated with Mycobacterium tuberculosis (8), and IL-32 acts synergistically with muramyl peptide (MDP) to induce IL-6 via caspase-1-dependent IL-1␤ (6).In vitro, cytokines such as macrophage colony-stimulating factor (M-CSF) induce differentiation of monocytes into macrophages (9), whereas a combination of GM-CSF and IL-4 induces differentiation into dendritic cells (DCs) (10-13). Cytokines such as IL-6 and IFN-␥ can modulate GM-CSF/IL-4-induced monocyte differentiation by switching from DCs to macrophages (10,14). Although IL-6 induces th...

Background: Confirmatory tests for failure of transfer of passive immunity (FTPI) in dairy calves require direct measurements of the serum immunoglobulin G concentration. Enzyme-linked immunosorbent assay (ELISA) has advantages over single radial immunodiffusion (SRID) in terms of cost and time.Objectives: To evaluate the agreement between ELISA and SRID, and to compare the diagnostic performance of ELISA with indirect methods, in the detection of FTPI in calves.Animals: One hundred and fifteen dairy calves (aged 0-10 days) from 23 calf-rearing facilities.Methods: Prospective, observational study. The agreement between SRID and ELISA was determined by the Bland-Altman method. Fixed bias (SRID À ELISA) was calculated. For comparison of the diagnostic performance of ELISA with indirect methods, sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) curves were calculated at cut-off values of 500 and 1,000 mg/dL.Results: The agreement between SRID and ELISA was 94%. Fixed bias (SRID À ELISA) was 140 AE 364 mg/dL. The AUC and sensitivity of ELISA at the cut-off value of 1,000 mg/dL were higher than those of indirect methods (Po.004). The specificity of ELISA at the cut-off value of 1,000 mg/dL was not higher than that of indirect methods, except for serum total protein concentration assay.Conclusion and Clinical Importance: ELISA exhibited good diagnostic performance and good agreement with SRID. ELI-SA is an adequate method for both screening and confirmatory tests for FTPI in dairy calves at the cut-off value of 500 mg/dL.

Interleukin-32 (IL-32

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