Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hematologic malignancies.

Interleukin-8 (LL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are cytokines/hematopoietic growth factor and are important mediators of inflammation and immune resoponse producing pathophysiological changes in human disease. Levels of IL-8 and GM-CSF in circulation of various hematologic diseases are unknown. To demonstrate their importance in lymphoproliferative disorders, we have measured the circulating levels of these two cytokines from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-8 and GM-CSF levels were determined by highly specific enzyme-linked immunosorbent assays. IL-8 levels were elevated in most patients with B-cell malignancies, B-cell CLL (B-CLL) and B-cell NHL (B-NHL) as well as in patients with HD. However, GM-CSF levels were higher in most patients with NHL (T-NHL and B-NHL) and HD. IL-8 was undetectable in T-cell malignancies (T-CLL and T-NHL), whereas GMCSF was undetectable from CLL (T-CLL and B-CLL). Of interest, IL-8 levels were correlated with white blood cell counts (WBC) in B-cell malignancies (B-CLL and B-NHL) but not in HD. These results suggest that both IL-8 and GMCSF may play an important role in pathophysiological changes in B-NHL and HD. IL-8 may be related with recruitment and activation of neutrophils, whereas, GM-CSF in proliferation and differentiation of hematopoietic progenitor cells and immune response in these malignancies. The clinical status of B-CLL patients in regards to WBC counts appeared to be associated with the serum levels of IL-8.

Peripheral T-cell lymphomas - cytokine profile and characteristic interleukin-4 and tumor-necrosis-factor alpha-deficiency.

Because of the recent evidence of involvement of cytokines in the inflammatory processes, cellular proliferation and host defence mechanism, we have measured the in vitro production of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-6 and tumor necrosis factor-alpha (TNFalpha) from the phenotypically and histologically characterized ten peripheral T cell lymphoma (PTCL) cases. The immunophenotypic study had identified three gammadelta PTCL cases (CD3-CD4+CD8+, one case and CD3+CD4-CD8, two cases). Mononuclear cells obtained from the lymph node cells of PTCL cases, irrespective of histologic type, were found to produce highly elevated levels of IFN-gamma and IL-6 both spontaneously and in response to concanavalin A stimulations. However, IL-4 and TNFalpha production was characteristically decreased from cells obtained from both blood and lymph nodes. IL-4 and TNFalpha have a number of pleiotropic activities in particular stimulation of various immune effector functions. Their deficient production is an important indication of severe immune dysfunction in this disease. However, the meaning of their deficient production is currently unclear. It may be a loss of physiologic regulation within the cytokine network. On the contrary, elevated IFN-gamma and IL-6 production may be important in etiology, inflammatory response or disease pathogenesis.

Visceral leishmaniasis with a very-low degree of bone-marrow parasitemia, mimicking malignant histiocytosis.

Visceral leishmaniasis (VL) is common in the Middle East, the Mediterranean region, East Africa and India. It is extremely rare in the west. Its manifestations can be protean with occasional cases presenting with features indistinguishable on clinical or even histological grounds from malignant disorders. We report here a unique case of VL who was diagnosed as malignant histiocytosis (MH) and planned to receive chemotherapy. The patient was an adult severely ill Sudanese who presented with a few months history of fever, cough, wasting, progressive splenomegaly, jaundice, pancytopenia and frank features of disseminated intravascular coagulopathy. Bone marrow examination revealed extensive infiltration by atypical hemophagocytosing histiocytes, consistent with malignant histiocytosis. The routine search for amastigotes of Leishmania was negative. An unexpected later positive serology for VL prompted us to search the bone marrow for Leishman-Donovan bodies. After ten hours of expert search we identified three conclusive parasites, the first one being detected after five hours of an intensive and compulsive microscopy. Diagnosis of VL was made and the patient was cured on anti-protozoal medications. We conclude that in endemic regions for parasitic disorders, unusual presentations of common protozoal problems are more common than rare malignant disorders. In leishmania endemic areas of the world, one should utilize all the possible diagnostic resources, and possibly stretch the routine search to its fullest, to confirm the diagnosis of VL and exclude MH. Perhaps this is one of the very few clinical situations in which histological diagnosis of a malignancy can be erroneous. VL should be excluded in every case of MH diagnosed in the geographical area of leishmaniasis.