A role for cytokines in early pregnancy.

Cytokines are expressed in a variety of cell types of the reproductive system, although in most instances their functions are not understood. There are, however, a few instances where a role in early pregnancy has been established. First, preimplantation conceptuses of ruminant ungulate species, such as cattle, sheep and goat, secrete a unique Type I interferon (IFN-tau). By mechanisms that are still unclear, IFN-tau prevents the destruction of the corpus luteum and hence ensures the continued production of progesterone which is essential for continuation of pregnancy. Most like the IFN-tau prevent lutcolysis by modulating the output of a luteolytic hormone, prostaglandin F2 alpha, from the uterus. Depsite this involvement in pregnancy, the IFN-tau possess similar antiproliferative and antiviral activities to other Type I IFN, 1 lambda e.g. IFN-alpha. There are 4-5 genes for IFN-tau in sheep and cattle whose promotor regions are highly conserved and distinct from those of other Type I IFN. These genens are not virally inducible and are expressed only in the trophectoderm (outer epithelium of the developing placenta) from the time of blastocyst hatching to implantation. Leukemia inhibitory factor (LIF) is a multi-functional cytokine which is expressed by uterine endometrium of pregnant mice around day 4 of pregnancy. Female mice lacking a functional LIF gene are fertile but their blastocysts fail to implant, strongly implicating the cytokine in maternal control of implantation. Colony stimulating factors (CSF) are a family of proteins (GM-CSF, CSF-1, G-CSF, and IL-3) that stimulate the cellular proliferation and induction of terminal differentiation of hemopoietic progenitor cells. CSF-1 is expressed in the uterine endometrium of the mouse and human during early pregnancy and its receptor, fms, is present on trophoblast. The osteopetrotic mouse, which represents a natural "knockout" of the CSF-1 gene, exhibits a low rate of fetal implantation and poor fetal viability. It seems likely that CSF-1 expression by the uterus influences growth and differentiation of the placenta. Although different species may utilize different strategies for ensuring developmental and endocrinological coordination between the embryo and the mother, these three examples illustrate that cytokines are likely to be major participants as autocrine factors that direct the events of early pregnancy and not simply as modulators of the maternal immune system.

Interferon producing capacity (IPCA) of peripheral mononuclear cell in oral cancer patients.

Interferon producing capacity (IPCA) of peripheral blood mononuclear cells is ability of these cells to produce IFN with suitable IFN inducer. In Vitro IPCA of cryopreserved mononuclear cells (MNC) from peripheral blood of 46 oral cancer patients was studied and was compared to that of healthy, age matched donors. New castle disease virus (NDV) and staphylococcal enterotoxin A (SEA) were used as inducers for evaluating Type alpha IPCA (AIPCA) and Type gamma IPCA (GIPCA) respectively. Age of healthy donors did not influence the AIPCA or GIPCA. Oral cancer patients demonstrated significant low AIPCA (P less than 0.05) (Range Healthy donors 3.5 to 4.6 log 10Iu/ml Oral Cancer 2.0 to 4.6 log 10Iu/ml GIPCA was found to be further depressed (P less than 0.005) (Range Healthy donors 2.87 to 3.6 Log 10 U/ml, Oral cancer 1.7 to 3.6 log 10 U/ml. The depression in IPCA was found to be more pronounced in advanced stage of disease.

Estudios sobre la producción de un Interferón recombinante alfa humano expresado bajo el control del promotor lac UV5 de Escherichia coli / Research on production of recombinant alpha human interferon expressed by control of lac UV5 promotor of Escherichia coli

La inserción de un oligonucleótido de 18 pares de bases en el sitio Pvull, ubicado en la región que codifica para el prepéptido del gen de IFN * 2 humano, resultó en un notable incremento en la actividad antiviral producida en E. coli bajo el control de los promotores lac UV5 situado en un plásmido recombinante. El máximo de actividad antiviral específica, cuando se utilizó E. coli HB 101 como célula hospedadora, se produjo en la mitad de la fase exponencial, después de lo cual se observó una marcada caída. Cuando se utilizó E. coli JM 101, que solo permite la síntesis del antiviral en presencia del inductor (IPTG), el máximo se observó una hora y media después de agregado este inductor, cualquiera fuere el punto de la curva de crecimiento. El contenido plasmídico por célula durante el ciclo de crecimiento se mantuvo constante. Cuando se amplificó el número de copias del plásmido por pretratamiento de las bacterias con cloranfenicol, se amplificó la capacidad de síntesis en los puntos iniciales de la curva de crecimiento. La vida media del antiviral en extractos bacterianos crudos fue de 75 minutos a 37-C y 165 minutos a 30-C. La disminución de la temperatura de cultivo de 37-C a 34-C durante la producción, aumentó la velocidad inicial de acumulación del producto, pero el máximo alcanzado en la actividad específica del antiviral no varió