Immunological findings in acute and chronic pancreatitis

Abstract

In order to identify the role of mononuclear cells in pancreatitis, the immune picture at the cellular level has been studied. The cytokine production at the individual cell level in response to in vitro stimulation can help in identifying the percentage of specific cell types producing a particular cytokine. A total of 30 patients with acute pancreatitis (AP; n = 15) and chronic pancreatitis (CP; n = 15) were entered into the study and peripheral blood samples were drawn at the time of admission. A control group of 12 healthy individuals (age and sex matched) were also included in the study. Mononuclear cells from the peripheral blood from all three groups were separated on Ficoll gradient and labelled for surface antigens (i.e. cluster of differentiation (CD)3, CD4, CD8, CD25, CD14 and human leucocyte antigen D receptor (HLA-DR)) using monoclonal antibodies. The CD3+ and CD14+ cells were also stained for intracellular cytokines by specific monoclonal antibodies (i.e. for interferon (IFN)-gamma, interleukin (IL)-2, IL-4 & IL-10 in CD3+ cells and IL-6 and IL-12 in CD14+ cells). These fluorochrome-labelled cells were analysed on the flow cytometer. The T-cell population is affected in pancreatitis where the CD4+ and CD8+ T-cell numbers are significantly altered. There is a marked reduction in CD4+ T cells in AP and CP. The CD8+ T cells were significantly reduced in AP. The IL-2 receptor is expressed in large numbers in AP and CP patient groups. The T cells from the CP group had a typical IL-2, IL-4 secreting pattern, while AP patients had a high IL-10, IFN-gamma and low IL-2, IL-4 population. The HLA-DR expression on monocytes differed significantly between the two groups, being strikingly reduced in chronic cases and significantly reduced in acute cases. The percentage of IL-6-producing monocytes was significantly higher in patients with AP as well as CP while IL-12 levels were higher in the CP than in the AP group. T cells in CP are polarized towards the T-helper (Th)1 phenotype while the AP patients had a mixed population. This seems to be a part of immune deviation that is associated with development of CP and IL-12 appears to be instrumental in this process. The monocytes synthesize proinflammatory cytokines, which play an important role in the local and systemic consequences of the disease. In the disease clinical assessment such a study can provide useful information about the involvement of the immuno-inflammatory system.