Biomedical subjects

R R Rowland

Publications and source records attributed to R R Rowland.

35 records · Page 2Linked to original sources

PubMed1995

Lactate dehydrogenase-elevating virus entry into the central nervous system and replication in anterior horn neurons.

The initial replication of lactate dehydrogenase-elevating virus (LDV) in mice, its invasion of the central nervous system (CNS) and infection of anterior horn neurons in C58 and AKXD-16 mice were investigated by Northern and in situ hybridization analyses. Upon intraperitoneal injection, LDV replication in cells in the peritoneum was maximal at 8 h post-infection (p.i.). Next, LDV infection was detected in bone marrow cells and then in macrophage-rich regions of all tissues investigated (12 to 24 h p.i.). By 2 to 3 days p.i., LDV RNA-containing cells had largely disappeared from all non-neuronal tissues due to the cytocidal nature of the LDV infection of macrophages. In the CNS at 24 h p.i. LDV replication was very limited and confined to cells in the leptomeninges. LDV replication in the cells of the leptomeninges should result in the release of progeny LDV into the cerebrospinal fluid and thus its dissemination throughout the CNS. However, in C58 and AKXD-16 mice, which are susceptible to paralytic LDV infection, only little LDV RNA and few LDV-infected cells were detectable in the spinal cord until at least 10 days p.i. Extensive cytocidal infection of anterior horn neurons occurred only shortly before the development of paralytic symptoms between 2 and 3 weeks p.i. The reason for the relatively long delay in LDV infection of anterior horn neurons is not known. No LDV RNA or LDV RNA-containing cells were detected in the brain, except in the leptomeninges at early times after infection.

Animals↗

PubMed1995

Infection of central nervous system cells by ecotropic murine leukemia virus in C58 and AKR mice and in in utero-infected CE/J mice predisposes mice to paralytic infection by lactate dehydrogenase-elevating virus.

Certain mouse strains, such as AKR and C58, which possess N-tropic, ecotropic murine leukemia virus (MuLV) proviruses and are homozygous at the Fv-1n locus are specifically susceptible to paralytic infection (age-dependent poliomyelitis [ADPM]) by lactate dehydrogenase-elevating virus (LDV). Our results provide an explanation for this genetic linkage and directly prove that ecotropic MuLV infection of spinal cord cells is responsible for rendering anterior horn neurons susceptible to cytocidal LDV infection, which is the cause of the paralytic disease. Northern (RNA) blot hybridization of total tissue RNA and in situ hybridization of tissue sections demonstrated that only mice harboring central nervous system (CNS) cells that expressed ecotropic MuLV were susceptible to ADPM. Our evidence indicates that the ecotropic MuLV RNA is transcribed in CNS cells from ecotropic MuLV proviruses that have been acquired by infection with exogenous ecotropic MuLV, probably during embryogenesis, the time when germ line proviruses in AKR and C58 mice first become activated. In young mice, MuLV RNA-containing cells were found exclusively in white-matter tracts and therefore were glial cells. An increase in the ADPM susceptibility of the mice with advancing age correlated with the presence of an increased number of ecotropic MuLV RNA-containing cells in the spinal cords which, in turn, correlated with an increase in the number of unmethylated proviruses in the DNA extracted from spinal cords. Studies with AKXD recombinant inbred strains showed that possession of a single replication-competent ecotropic MuLV provirus (emv-11) by Fv-1n/n mice was sufficient to result in ecotropic MuLV infection of CNS cells and ADPM susceptibility. In contrast, no ecotropic MuLV RNA-positive cells were present in the CNSs of mice carrying defective ecotropic MuLV proviruses (emv-3 or emv-13) or in which ecotropic MuLV replication was blocked by the Fv-1n/b or Fv-1b/b phenotype. Such mice were resistant to paralytic LDV infection. In utero infection of CE/J mice, which are devoid of any endogenous ecotropic MuLVs, with the infectious clone of emv-11 (AKR-623) resulted in the infection of CNS cells, and the mice became ADPM susceptible, whereas littermates that had not become infected with ecotropic MuLV remained ADPM resistant.

Animals↗

PubMed1995

Lactate dehydrogenase-elevating virus replication persists in liver, spleen, lymph node, and testis tissues and results in accumulation of viral RNA in germinal centers, concomitant with polyclonal activation of B cells.

Lactate dehydrogenase-elevating virus (LDV) replicates primarily and most likely solely in a subpopulation of macrophages in extraneuronal tissues. Infection of mice, regardless of age, with LDV leads to the rapid cytocidal replication of the virus in these cells, resulting in the release of large amounts of LDV into the circulation. The infection then progresses into life-long, asymptomatic, low-level viremic persistence, which is maintained by LDV replication in newly generated LDV-permissive cells which escapes all antiviral immune responses. In situ hybridization studies of tissue sections of adult FVB mice revealed that by 1 day postinfection (p.i.), LDV-infected cells were present in practically all tissues but were present in the highest numbers in the lymph nodes, spleen, and skin. In the central nervous system, LDV-infected cells were restricted to the leptomeninges. Most of the infected cells had disappeared at 3 days p.i., consistent with the cytocidal nature of the LDV infection, except for small numbers in lymph node, spleen, liver, and testis tissues. These tissues harbored infected cells until at least 90 days p.i. The results suggest that the generation of LDV-permissive cells during the persistent phase is restricted to these tissues. The continued presence of LDV-infected cells in testis tissue suggests the possibility of LDV release in semen and sexual transmission. Most striking was the accumulation of large amounts of LDV RNA in newly generated germinal centers of lymph nodes and the spleen. The LDV RNA was not associated with infected cells but was probably associated with virions or debris of infected, lysed cells. The appearance of LDV RNA in germinal centers in these mice coincided in time with the polyclonal activation of B cells, which leads to the accumulation of polyclonal immunoglobulin G2a and low-molecular-weight immune complexes in the circulation.

Animals↗

PubMed1995

Cytotoxic T cells are elicited during acute infection of mice with lactate dehydrogenase-elevating virus but disappear during the chronic phase of infection.

Lactate dehydrogenase-elevating virus (LDV) invariably establishes a life-long viremic infection in mice, which is maintained by replication of LDV in a renewable subpopulation of macrophages and escape from all host immune responses. We now demonstrate that cytotoxic T lymphocytes (CTLs) that specifically lyse LDV-infected macrophages and 3T3 cells producing the nucleocapsid protein of LDV were elicited in Swiss, B10.A, and (Swiss x B10.A)F1 mice. To detect target cell lysis, splenocytes needed to be expanded by a 5-day in vitro culture in the presence of recombinant interleukin 2 and syngeneic LDV protein-expressing cells. In vitro culture resulted in the specific expansion of CD8+ cells which mediated the lysis of target cells in a major histocompatibility complex class I-restricted manner. When CTLs were added to macrophage cultures at 1 h after infection with LDV, the lysis of the infected macrophages by the CTLs started about 5 h postinfection (p.i.) and, at an effector cell/target cell ratio of 25:1, resulted in the lysis of all LDV-infected macrophages in a culture by about 7 h p.i. However, lysis of the LDV replication in a culture was not rapid enough to significantly suppress the LDV yield in the culture. LDV replication in mice was also little affected by the presence of CTLs which were induced by immunization with 3T3 cells expressing the LDV nucleocapsid protein. Furthermore, all CTL precursor cells in infected mice had disappeared by 30 days p.i. Loss of CTL precursor cells in infected mice probably reflected high-dose clonal exhaustion, since LDV infection of a mouse results in massive production of LDV in all tissues of the mouse, but especially in lymphoidal tissues, and accumulation of LDV in newly formed germinal centers. Furthermore, slow LDV replication continues in the thymus and other lymphoidal organs.

3T3 Cells↗

PubMed1995

C58 and AKR mice of all ages develop motor neuron disease after lactate dehydrogenase-elevating virus infection but only if antiviral immune responses are blocked by chemical or genetic means or as a result of old age.

Age-dependent poliomyelitis is a paralytic disease of C58 and AKR mice caused by cytocidal infection of anterior horn neurons with neuropathogenic strains of lactate dehydrogenase-elevating virus (LDV). The motor neurons are rendered LDV-permissive via an unknown mechanism through the expression of ecotropic murine leukemia virus (MuLV) in central nervous system (CNS) glial cells. Only old mice develop paralytic disease after LDV infection, but mice 5-6 months old or older can be rendered susceptible by suppression of anti-LDV immune responses by a single treatment with cyclophosphamide or X-irradiation before LDV infection. Younger mice appeared to be resistant in spite of this immunosuppresive treatment. The present results confirm that mice as young as 1 month of age possess CNS cells expressing ecotropic MuLV and show that these mice are susceptible to paralytic LDV infection provided their anti-LDV immune responses are blocked for an extended period of time by repeated cyclophosphamide treatments or by a genetic defect. Furthermore, old mice become naturally susceptible to paralytic LDV infection because of an impaired ability to mount a motor neuron protective anti-LDV immune response.

Aging↗

PubMed1994

Nitric oxide production by splenic macrophages is not responsible for T cell suppression during acute infection with lactate dehydrogenase-elevating virus.

Cellular immune responses of mice are transiently suppressed during acute infection with lactate dehydrogenase-elevating virus (LDV). Immunosuppression of mice correlated with a greatly impaired in vitro proliferative response of the majority of the T cells to Con A or anti-CD3 Abs, which could not be reversed by the addition of rIL-2. We have examined whether the T cell suppression is caused by nitric oxide (NO) produced by activated macrophages, which are observed in acutely infected mice. Spleen macrophages from 3-day LDV-infected mice exhibited a 6- to 10-fold increased potential for producing NO, measured as nitrite or nitrite plus nitrate in the culture fluid, but produced significant amounts of NO in vitro only when incubated with IFN-gamma produced by Con A-stimulated T cells in the spleen cell population. Furthermore, we found that the concentrations of NO produced by macrophages in cultures of spleen cells from LDV-infected mice in the presence of IFN-gamma were insufficient to cause a reduction in the proliferative response of T cells in the spleen cell population. An excess of activated macrophages had to be added to achieve T cell suppression. NO inhibition of Con A-induced T cell proliferation exhibited a very sharp dose-response curve. In one experiment little suppression was observed at NO concentrations equivalent to 12 microM nitrite and below, whereas almost complete inhibition was observed at twice the NO concentration. We conclude that NO is not responsible for T cell suppression in LDV-infected mice.

Animals↗

PubMed1994

Neonatal infection of mice with lactate dehydrogenase-elevating virus results in suppression of humoral antiviral immune response but does not alter the course of viraemia or the polyclonal activation of B cells and immune complex formation.

Neonatal infection of FVB mice with lactate dehydrogenase-elevating virus (LDV) prevented the normal formation of anti-LDV antibodies observed in mice infected at 5 days of age or older. Even 22 weeks post-infection, the concentration of circulating anti-LDV antibodies in neonatally infected mice was insignificant. However, the time course and level of persistent viraemia were the same in neonatally infected mice lacking anti-LDV antibodies as in mice infected at 5 or 15 days of age which developed normal antiviral immune responses. The results support the view that LDV replication in mice is unaffected by antiviral immune responses and instead is primarily dependent on the rate of regeneration of LDV-permissive macrophages. This view is further supported by the following findings. Treatment of mice with cyclophosphamide or dexamethasone, which are known to increase plasma LDV levels, increased the proportion of LDV-permissive macrophages in the peritoneum. Injection of mice with interleukin-3, which is known to stimulate macrophage development, increased plasma LDV levels in persistently infected mice 10- to 100-fold. During the first month of age when mice possess a higher proportion of LDV-permissive macrophages than older mice and peritoneal macrophages exhibit self-sustained growth, the persistent plasma LDV titres were also 10- to 100-fold higher than in older mice. The polyclonal activation of B cells induced by LDV that results in a permanent elevation of IgG2a or IgG2b in the circulation, and the formation of 180K to 300K immune complexes containing IgG2a or IgG2b were also the same in neonatally infected mice and mice infected 5 or 15 days after birth. Thus, the polyclonal activation of B cells occurs in the absence of an antiviral humoral immune response and the immune complexes do not contain anti-LDV antibodies. The immune complexes probably consist of autoantibodies formed in the course of the polyclonal activation of B cells and their cellular antigens.

Animals↗

PubMed1993

Sequences of 3' end of genome and of 5' end of open reading frame 1a of lactate dehydrogenase-elevating virus and common junction motifs between 5' leader and bodies of seven subgenomic mRNAs.

The sequences of the 3'-terminal 3.7 kb of the genome and of a 1.7 kb 5' end cDNA clone of one isolate of lactate dehydrogenase-elevating virus (LDV) are reported. The 3' end sequence encodes six major independent open reading frames (ORFs 2 to 7), which are overlapping by between one and 130 nucleotides. Each ORF is expressed at the 5' end of one of six 3'-coterminal subgenomic mRNAs (mRNAs 2 to 7, respectively; 3.5 to 0.8 kb). The smallest mRNA, mRNA 7, encodes the nucleocapsid protein, VP1; mRNA 6 probably encodes the non-glycosylated envelope protein, VP2; and mRNAs 2 to 5 encode proteins of 26.0K, 21.5K, 19.2K and 22.4K, respectively, each possessing several potential N-glycosylation sites and membrane-spanning segments. About 72% of the LDV genome segment carrying ORFs 2 to 7 exhibits about 50% or higher nucleotide identity with the corresponding genome segment of swine infertility and respiratory syndrome (Lelystad) virus (LV), whereas only limited similarity is observed in discontinuous regions of the same corresponding genome segments of LDV and equine arteritis virus (EAV). EAV and LV belong to the same new group of positive-strand RNA viruses as LDV. One additional subgenomic mRNA of about 4 kb is produced in LDV- but not in EAV- or LV-infected cells. The 5' end of this mRNA (1-1) carries a continuous coding sequence. The N-terminal 80 amino acids of the predicted product exhibit about 50% identity with segments in the ORF 1b proteins of both EAV and LV. These segments are located 117 to 150 amino acids upstream of the C termini of the ORF 1b proteins of these viruses. The 5' end cDNA clone contains part of a 5' leader associated with all seven subgenomic mRNAs and the 5' end of ORF 1a. The junctions between the 5' leader and the bodies of all seven subgenomic mRNAs have been determined. Only a single junction sequence was detected for each mRNA. Linkage occurs between a 5' UAUAACC 3' sequence at the 3' end of the leader and only partially identical segments specified downstream in the genome preceding ORFs 2 to 7. The generated junctions differ for different subgenomic mRNAs but possess the consensus sequence 5' U(A/G)(U/A)AACC 3'. In mRNA 7, the UA in positions 1 and 2 are derived from the leader, but a G in position 2 in mRNAs 1-1, 3 and 4 and an A in position 3 in mRNA 6 seem to be specified by the 3' genomic sequences.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1993

DNA polymerase I and the bypassing of RecA dependence of constitutive stable DNA replication in Escherichia coli rnhA mutants.

In Escherichia coli rnhA mutants, several normally repressed origins (oriK sites) of DNA replication are activated. The type of DNA replication initiated from these origins, termed constitutive stable DNA replication, does not require DnaA protein or the oriC site, which are essential for normal DNA replication. It requires active RecA protein. We previously found that the lexA71(Def)::Tn5 mutation can suppress this RecA requirement and postulated that the derepression of a LexA regulon gene(s) leads to the activation of a bypass pathway, Rip (for RecA-independent process). In this study, we isolated a miniTn10spc insertion mutant that abolishes the ability of the lexA(Def) mutation to suppress the RecA requirement of constitutive stable DNA replication. Cloning and DNA sequencing analysis of the mutant revealed that the insertion occurs at the 3' end of the coding region of the polA gene, which encodes DNA polymerase I. The mutant allele, designated polA25::miniTn10spc, is expected to abolish the polymerization activity but not the 5'-->3' or 3'-->5' exonuclease activity. Thus, the Rip bypass pathway requires active DNA polymerase I. Since the lethal combination of recA(Def) and polA25::miniTn10spc could be suppressed by derepression of the LexA regulon only when DNA replication is driven by the oriC system, it was suggested that the bypass pathway has a specific requirement for DNA polymerase I at the initiation step in the absence of RecA. An accompanying paper (Y. Cao and T. Kogoma, J. Bacteriol. 175:7254-7259, 1993) describes experiments to determine which activities of DNA polymerase I are required at the initiation step and discusses possible roles for DNA polymerase in the Rip bypass pathway.

Amino Acid Sequence↗

PubMed1992

Evidence of altered T-lymphocyte number and proliferative responses in genetically epilepsy-prone rats.

Genetically epilepsy-prone (GEPR-9) rats exhibit decreased antibody plaque-forming cell responses following immunization. We examined the hypothesis that this immunosuppression was due to deficits in the number or proliferative responses of T-lymphocytes. Splenocyte responses to concanavalin A and pokeweed mitogen were significantly greater in GEPR-9 rats than controls. Flow cytometric analysis indicated that GEPR-9 rats possess an increase in T-cells associated with the T-helper phenotype. The increased proportion of T-helper cells in GEPR-9 rats may underlie their enhanced proliferative responses to T-cell mitogens. These results clearly indicate that the failure of the GEPR-9 rat to respond to a T-dependent antigen in vivo is not due to a lack of T-helper activity.

Animals↗

PubMed1992

Lactate dehydrogenase-elevating virus (LDV): subgenomic mRNAs, mRNA leader and comparison of 3'-terminal sequences of two LDV isolates.

The 3'-terminal 1314 nucleotides of the genome of one isolate of lactate dehydrogenase-elevating virus, LDV-P, has been derived by sequence analyses of cDNAs from several genomic libraries and compared to that of another LDV isolate, LDV-C (Godeny et al. (1990) Virol. 177, 768-771). The 3'-non-coding segment of 80 nucleotides of the two LDV genomes is identical, whereas marked, but varying nucleotide and amino acid divergence is apparent in the three upstream overlapping open reading frames (ORF). The third ORF from the 3'-end exhibits only 82% nucleotide and 90% amino acid identity, whereas the 3'-terminal ORF, which encodes the nucleocapsid protein, exhibits approximately 99% amino acid identity. The second 3'-terminal ORF encodes an 18.8 kDa protein which lacks N-glycosylation sites but possesses 2 or 3 potential transmembrane helices in the N-terminal half of the molecule. A similar membrane organization is observed for the corresponding protein of equine arteritis virus and the M protein of mouse hepatitis virus. The sequence analyses combined with Northern hybridization analyses of RNA from LDV-infected macrophages and spleens of LDV-infected mice indicate that the three ORFs encoded by the 3'-terminal end of the LDV genome are expressed via the three smallest mRNAs (mRNAs 6-8) of the seven subgenomic mRNAs of LDV (mRNAs 2-8), which range in size from about 0.8 to 3.6 kb. All mRNAs have been shown to carry poly(A)-tracts and a common leader sequence. The seven mRNAs were produced in infected macrophage cultures concomitantly with genomic LDV RNA. Maximum LDV RNA synthesis was observed between 6 and 8 h post-infection. The same seven subgenomic mRNAs were detected in macrophages infected with three different isolates of LDV, but different relative amounts of some of the mRNAs were produced. The relative proportions of molecules of mRNAs 1-8 present in 6 h LDV-P-infected macrophages were about 13, 5, 5, 8, 6, 11, 11 and 27% of the total, respectively.

Amino Acid Sequence↗

PubMed1991

Evidence of immunosuppression in the genetically epilepsy-prone rat.

Immune system function was examined in the genetically epilepsy prone (GEPR-9) rat and non-epileptic Sprague-Dawley control rats. Significant decreases in direct and indirect plaque-forming cell responses were observed in GEPR-9 rats immunized with sheep erythrocytes. Serum levels of IgM were also decreased in non-immunized GEPR-9 rats, providing additional evidence of immunosuppression. However, total serum levels of IgG were three-fold greater in GEPR-9 rats compared to control. These results suggest that the nature of the immune system deficit in the GEPR-9 is complex and may involve an active T-cell population stimulating an overproduction of IgG leading to a diminished capacity to respond to new antigen challenges. This immunological defect may underlie the enhanced susceptibility of GEPR-9 rats to infectious agents. The specific cause of this immune dysfunction is not known. Possible etiological factors include a breakdown in the communication between cells within the immune system or an alteration of neuroendocrine modulation of immune responses.

Animals↗

PubMed1989

Dual immunomodulation by met-enkephalin.

Met-enkephalin (MENK) is an opioid peptide that is released during physiological stress and is reported to either up-regulate or down-regulate the immune response. Our previous experiments showed the ability of 10(-7) M MENK to modulate the plaque-forming cell (PFC) response of Mishell-Dutton cultures treated with low, optimal, and large concentrations of sheep erythrocyte (SE) antigen. In the present series of experiments the PFC response was measured in splenocyte cultures challenged with incremental concentrations of SE in the presence of 10(-7) M MENK. These experiments illustrate what we consider to be true modulation, i.e., the ability of MENK to modulate immune function only during the presence of a strong immune signal. When the immune signal was strong, as represented by a strong PFC response, MENK suppressed the PFC response. Conversely, when the strongest immune signal was high-antigen suppression of the PFC response, MENK overcame the suppression and frequently returned the PFC response to a greater than optimal level. In a true modulatory fashion MENK had no effect in those regions of the dose-response curve where there was insufficient antigen to induce a strong immune signal.

Animals↗

PubMed1987

Modulation of the in vitro murine immune response by met-enkephalin.

The in vitro priming of mouse spleen cultures with sheep erythrocytes (SE) was used to study the modulation of immune function by met-enkephalin (MENK). In these studies, suboptimal, optimal, and supraoptimal concentrations of SE were used to manipulate the plaque-forming cell (PFC) responses of cultured spleen cells. MENK, at a concentration of 10(-7) M, was able to abolish the high antigen dose-induced suppression of the PFC response, but was unable to increase the PFC response of cultures treated with suboptimal doses of antigen. On rare occasions when the supraoptimal dose of antigen did not suppress the immune response, the addition of 10(-7) M MENK to the culture medium suppressed the PFC response. Naloxone was unable to block the effect of MENK. These results indicate that the nature of the immune response must be taken into consideration when evaluating the effect of opioid peptides on immune function. We propose that MENK possesses a dual modulatory role, with the abilities to suppress a strong immune response and reverse high antigen-induced immunosuppression.

Animals↗

PubMed1986

Early detection of extravascular lung water in an inhalation injury animal model.

A rabbit inhalation injury model using a dual tracer radioactive isotope technique (Rowland et al., 1986), has been utilized with small- and medium-sized molecular weight tracers. There is oedema formation at 2 h after smoke inhalation or fluid resuscitation and especially with the combination of inhalation injury and fluid resuscitation [corrected]. This oedema appears to have decreased by 24 h post-injury. There does not appear to be any difference between the small- and medium-sized tracers in the transit times of tracer in the lung vascular compartment. The increases in extravascular water volume have been confirmed by gravimetric analyses of the lungs. Thus the pulmonary oedema in the rabbit animal model is detectable within 2 h post-injury, with a return towards normal values some time within 24 h if fluid challenged for short periods. Fluid resuscitation exacerbates the amount of oedema that developed. The onset of pulmonary oedema may therefore be earlier than previously seen clinically, and fluid resuscitation modifications may be of benefit in smoke inhalation injury.

Animals↗

PubMed1986

Smoke inhalation model for lung permeability studies.

The purpose of this project was the development of a small animal model and the use of external gamma imaging for the study of acute post-inhalation permeability changes. New Zealand white rabbits were anesthetized with ketamine and acepromazine IM, intubated, and a catheter placed in an ear artery. Smoke was produced by burning absorbent cotton in a combustion chamber supplied with 10 liters/min of air. Smoke was delivered to a holding chamber, allowed to cool to room temperature, and immediately delivered to the animals via endotracheal tube. Animals were allowed to inhale smoke for 3 sessions of 2 to 3 minutes. Blood samples were collected for the measurement of PO2, PCO2, and COHb. Lungs were removed at 3 to 4 days postinjury and subjected to microscopic histologic analysis. The results of six animal experiments showed a significant inhalation injury. The mean COHb level was 48% (range, 36%-58%). The change in the pre- and post-injury PO2 and PCO2 values were not significant (mean PO2, 66 mm Hg; mean PCO2, 32 mm Hg). Histologic evaluation of the lungs of three animals at 24 hrs postinjury revealed extensive loss of tracheal epithelium extended to many terminal bronchi. Inflammation of surrounding tissue, including edema and increased migration of polymorphonuclear cells, was also present. Analysis of tissue obtained at 10 to 14 days showed reparative reepithelialization of trachea and major bronchi but acute inflammation and loss of intralobar bronchi. Inflammatory exudate extended to adjacent alveoli. In conjunction with the above model we have developed a method for the noninvasive measurement of lung permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Corticosteroid and immune responses of mice following mini-osmotic pump implantation.

Serum corticosteroid (CS) levels were measured in (B6xA)F1 mice following the implantation of ALZET mini-osmotic pumps. Studies of shipment stress were used as a basis for comparison. At 24 and 48 h following the implantation of pumps CS levels were moderately elevated. However, immunization of animals at 24 h postsurgery with sheep erythrocytes showed normal immune responses. The results of these experiments indicate that the use of mini-osmotic pumps for the delivery of immunomodulatory drugs induces moderate and short-term increases in CS levels, which do not appear to interfere with normal immune function.

Adrenal Cortex Hormones↗