Hydrocortisone inhibits granulocyte-macrophage colony-stimulating factor production from normal human peripheral blood mononuclear cells and CD3+ T cells.

Normal human peripheral blood mononuclear cells (MNCs), particularly T lymphocytes (T cells), are a rich source of granulocyte-macrophage colony-stimulating factor (GM-CSF). Glucocorticoids are known to inhibit GM-CSF production in in vitro cultures of a human fibroblast cell line and in normal human blood monocytes and alveolar macrophages. To determine whether glucocorticoids also inhibit GM-CSF production from normal human MNCs and T cells, we set up cultures of normal human MNCs and T cells in a liquid system in the presence and absence of 5, 50, and 250 microg/dL of hydrocortisone, and an hour later, a constant dose of 50-ng/mL Escherichia coli lipopolysaccharide (LPS) or 10-microg/mL phytohemagglutinin (PHA) was added. After three days, cell counts and GM-CSF levels were determined. Administering 50- and 250-microg/dL hydrocortisone decreased lymphocyte recovery from MNC cultures with LPS (p < or = 0.01), and 250 microg/dL of hydrocortisone decreased lymphocyte recovery from MNC and T-cell cultures with PHA (p < or = 0.03). The amount of GM-CSF produced from PHA-stimulated MNCs was about 100-fold higher than that produced from LPS-stimulated MNCs. The magnitude of GM-CSFs produced in MNC and T-cell cultures stimulated by PHA was comparable (p=0.88). Administering hydrocortisone at 5, 50, and 250 pg/dL decreased GM-CSF production (p < 0.003) in LPS- or PHA-stimulated MNC cultures and in PHA-stimulated T-cell cultures. PHA (not tested with LPS)-stimulated GM-CSF messenger RNA (mRNA) expression was blocked by hydrocortisone. These results indicate that lower concentrations of hydrocortisone inhibit GM-CSF production from normal human blood MNCs and T cells entirely by inhibiting the expression of GM-CSF mRNA, and higher concentrations of hydrocortisone inhibit by a combined effect of inhibiting the expression of GM-CSF mRNA and decreasing the lymphocyte count.

The spleen: a correlative overview of normal and pathologic anatomy.

The human spleen, an organ of unique anatomic and functional importance, is the largest component of the reticuloendothelial system, with direct interposition between systemic and portal circulation, and yet the morphologic correlates of its various functions remain somewhat mysterious. The contributions of transmission and scanning electron microscopy to the understanding of splenic structure have been considerable. They have helped clarify the three fundamental sites of structural alteration and specialization that are defined and discussed: 1) the white pulp with its two variable components--the lymphoid follicle and periarteriolar sheath--which, with the marginal zone of the red pulp, is the primary site of lymphoproliferative activity; 2) the cords of the red pulp, the functionally slow component of the splenic circulation, which sequester senescent or structurally altered red cells and effect their removal by means of scavenging macrophages (and which may be secondarily involved by the accumulation of platelets or certain types of leukemic cells, resulting in chronic cordal distention, or by the accumulation of collagen in fibrocongestive splenomegaly); and 3) the splenic sinuses, the unique structure of which determines that only healthy red cells with normally plastic and flexible membranes pass through to the venous circulation. Abnormal transiting cells such as sickle cells frequently clog the apertures to these sinuses. Direct arteriocapillary sinus terminations provide the anatomic basis for a fast component of the red pulp circulation, the existence of which was questioned for many years and the extent of which is still unknown in pathologic states.

Central nervous system vasculitis in cytomegalovirus infection.

A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia. Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved. Tissue surrounding the foci of necrosis contained cells with intranuclear an intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 micrometer in diameter and were located in enlarged cells. Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus. The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed.