Interaction of recombinant IL-1 and recombinant tumor necrosis factor in the induction of mouse acute phase proteins.

Recombinant mouse and human IL-1 (alpha and beta forms), as well as rTNF-alpha when administered in vivo, induced the production of the mouse acute phase reactants: serum amyloid P-component (SAP), C3, and fibrinogen. The SAP response to all three rIL-1 proteins reached a maximum at a dose of 10(4) U/mouse, which corresponds to 1 to 10 micrograms of protein. The maximum in vivo response consisted of a 10-fold increase in SAP levels, a 2-fold increase in C3 levels, and a 3-fold increase in fibrinogen concentration.

Interdependence of the radioprotective effects of human recombinant interleukin 1 alpha, tumor necrosis factor alpha, granulocyte colony-stimulating factor, and murine recombinant granulocyte-macrophage colony-stimulating factor.

Interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), granulocyte-colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) are molecularly distinct cytokines acting on separate receptors. The release of these cytokines can be concomitantly induced by the same signal and from the same cellular source, suggesting that they may cooperate. Administered alone, human recombinant (hr)IL-1 alpha and hrTNF alpha protect lethally irradiated mice from death, whereas murine recombinant GM-CSF and hrG-CSF do not confer similar protection.

The in vivo effects of interleukin 1. I. Bone marrow cells are induced to cycle after administration of interleukin 1.

We have previously reported that interleukin 1 (IL-1) administration 20 hr before irradiation protects mice from lethal effects of radiation. The recovery of total nucleated bone marrow cells and of hematopoietic progenitor cells was enhanced in IL-1 treated, as compared to untreated, irradiated mice. This suggested that IL-1 administration may affect the cells in the bone marrow of normal mice.

Induction of colony stimulating factor in vivo by recombinant interleukin 1 alpha and recombinant tumor necrosis factor alpha 1.

In response to a potent inflammatory challenge, such as Gram-negative endotoxin, a number of cytokines are induced that, in turn, mediate many of the pathophysiologic alterations associated with endotoxicity. In this study, we have observed two endotoxin-associated monokines, recombinant interleukin-1 alpha (rIL 1 alpha) and recombinant tumor necrosis factor alpha (rTNF alpha), to induce colony stimulating factor (CSF) in vivo. The CSF activities produced in response to rIL 1 alpha or rTNF alpha gave rise to a mixture of granulocyte-macrophage colonies and were induced in a dose- and time-dependent fashion, peaking within 3 hr of cytokine injection (preceding peak CSF induction by endotoxin by several hours).

Tumor necrosis factor/cachectin is a less potent inducer of serum amyloid A synthesis than interleukin 1.

Serum amyloid A (SAA) gene expression is known to be induced by interleukin (IL-1). The time course of in vivo induction of SAA synthesis by IL-1 was found to vary according to dose, in that SAA concentration was maximal at 6 hours following lower doses of IL-1, but greater at 20 hours when higher (greater than 500 ng) doses were administered. Because of recent reports that recombinant human tumor necrosis factor/cachectin (TNF) is a pyrogen similar to IL-1, its efficacy as an inducer of SAA synthesis was analyzed.

Enhanced hematopoietic recovery in irradiated mice pretreated with interleukin-1 (IL-1).

Data in this report compare the number of colony-forming cells (CFC) in bone marrow from irradiated and pre-irradiated C57Bl/6J mice injected with saline or recombinant interleukin-1-alpha (rIL-1). Eight to 12 days after sublethal or lethal irradiation, there were more CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units erythroid), GM-CFC (granulocyte-macrophage colony-forming cells), and day 8 CFU-S (colony-forming units-spleen) in bone marrow from rIL-1 injected mice than from saline injected mice. Prior to irradiation, there was no increase in number of CFC in bone marrow from rIL-1 injected mice.

Interleukin 1 is a radioprotector.

Pretreatment with recombinant interleukin 1 (IL 1) protects mice in a dose-dependent manner from lethal effects of ionizing radiation. Two thousand units of IL 1, given i.p.

Cytokines in radioprotection. Comparison of the radioprotective effects of IL-1 to IL-2, GM-CSF and IFN gamma.

Immunomodulatory agents are radioprotective when administered to animals prior to irradiation. The mechanisms for this radioprotection have as yet not been determined, but may involve endogenously released cytokines. We have recently demonstrated that murine IL-1 is radioprotective in mice (Neta et al.

Thymic hormones in radiation-induced immunodeficiency. I. Induction of mature interleukin 1 responsive cell in the thymus by thymosin fraction 5.

The restorative effect of thymosin fraction 5 (TF5) on the thymus of gamma-irradiated mice was examined. Four different mouse strains were used in this study since earlier work determined that the degree of response to TF5 is strain dependent. The responsiveness to comitogenic effect of interleukin 1 (IL-1) was used to measure the rate of recovery of immunocompetent cells in the thymus, since only more mature PNA-, Lyt-1+-2- medullary cells respond to this monokine.

Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis.

Current concepts of pulmonary sarcoidosis suggest that the alveolar macrophage plays a central role in the pathogenesis of the disease. To help define the population of alveolar macrophages in sarcoidosis, we compared the surface phenotype of alveolar macrophages from patients with sarcoidosis and from normal individuals by using monoclonal antibodies (63D3, OKM1, M phi P-9, M phi S-1, 61D3, and M phi S-39) that detect surface antigens on cells of monocyte/macrophage lineage. Although almost all blood monocytes expressed surface antigens detected by each of these antibodies, only a minority of normal alveolar macrophages expressed the same surface antigens (p less than 0.