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Biomedical subjects

M Giovarelli

Publications and source records attributed to M Giovarelli.

108 records · Page 6Linked to original sources
PubMed1977

Effect of anti-mu-chain-specific immunosuppression on Chikungunya virus encephalitis of mice.

Mice neonatally immunosuppressed with anti-mu antiserum failed to produce circulating antibodies to sheep erythrocytes and showed a marked decrease in circulating immunoglobulins. However, when they were intracerebrally infected with Chikungunya virus (a group A togavirus), they showed a mortality rate consistently lower than non-immunosuppressed control mice. Several possible explanations for this finding are discussed.

Animals↗
PubMed1976

Induction of resistance or enhancement to a transplantable murine plasmacytoma by transfer of non-immune leucocytes.

Newborn mice have a lower spontaneous resistance to the growth of a syngeneic plasmacytoma (MOPC-460) as compared to adult mice. The transfer of different leucocyte populations from non-immunized adult donors to newborn mice influence in a dual way the resistance to MOPC-460 growth, depending on the number of cells transferred. The transfer of a low number of neutrophils, thymus or spleen cells enhances the MOPC-460 takes. Higher numbers of neutrophils, thymus or bone marrow cells induce an effective protenction. By contrast, macrophages over a dose of 1 X 10(4) constantly produce a reduction of tumour growth.

Animals↗
PubMedDate not supplied

Interleukin-2 injected around tumor-draining lymph nodes in head and neck cancer.

Twenty patients with recurrent, inoperable head and neck squamous cell carcinoma received perilymphatic injections of natural interleukin-2 (nIL-2) for 10 days. Ten patients received 200 units (U) of nIL-2; five 1,000 U; and five 5,000 U. Irrespective of the location of the recurrence, the injections were always performed 1.5 cm below the insertion of the sternocleidomastoid muscle on the mastoid. When the ipsilateral lymphatic chain was still present, they were performed on the same side as the tumor site, whereas when it had been stripped as a result of previous surgery, they were contralateral. Patients who had undergone bilateral neck dissection were injected on the tumor side. Whenever possible, the treatment was repeated after 45-day intervals. In 13 patients (65%) with bilateral or contralateral lymph nodes, complete or partial disappearance of the lesion was observed. Despite these marked responses, the tumor always relapsed, and subsequent IL-2 courses were poorly effective. There were no systemic disturbances during or after treatment, but only moderate local swelling and pain.

Adult↗
PubMedDate not supplied

Interferon-gamma plays a crucial role in T lymphocyte reaction against alloantigens.

In this study we report that addition to mixed lymphocyte reactions of monoclonal antibodies to interferon-gamma inhibits alloantigen recognition and induction of cytotoxic T lymphocytes by inducing early and highly effective suppressor T lymphocytes. This inhibitory activity is not confined to in vitro models, since daily local injection of these antibodies in CBA/J mice blocks the rejection of fully allogeneic tumor cells consistently displayed by untreated CBA/J mice.

Animals↗
PubMedDate not supplied

Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cell activity in mice.

Natural killer (NK) cells have an important role in non-adaptative resistance to tumours and their metastatic spread in vivo. Maturation of NK cells and the intensity of their activity are affected by many endogenous and external factors, as well as by regulatory cells. The possibility that some effects of the central nervous system on tumour resistance are mediated via NK activity has also been suggested. Destruction of the tuberoinfundibular region of the hypothalamus in rodents led to a significant increase in tumour growth. We show here that destruction of its ventromedial, dorsomedial and arcuate nuclei persistently abrogates NK activity in mice. By contrast, cortical lesion and operative stress depress it partially, and for a brief period only. Abrogation is the result of a block of NK lineage maturation, causing a severe decrease in the number of large granular lymphocytes (LGL), a lymphocyte population associated with NK activity. Macrophage, B- and T- lymphocyte functions, however, are not significantly affected. Agents inducing NK-cell maturation or activation such as polyinosinic-polycytidylic acid (poly(I:C], interferon (IFN) and interleukin-2 (IL-2) restore NK activity, and normalize the number of LGL.

Animals↗
PubMedDate not supplied

IL-10 enhances CCL2 release and chemotaxis induced by CCL16 in human monocytes.

CCL16 is a CC chemokine originally identified as a liver-expressed chemokine. Its expression has been detected in activated monocytes where it is up-regulated by stimulation with IL-10. This is in contrast with IL-10's inhibition of the expression of most chemokines. CCL16 is chemotactic for monocytes, lymphocyte and dendritic cells. We investigated whether CCL16 displays biological activities other than chemotaxis and whether IL-10 affects monocyte response to CCL16. We show that CCL16 induces the expression of CCL2 at the mRNA and protein level, but does not affect that of CCL5, CCL18 and proinflammatory cytokines. This effect was prevented by treatment with pertussis toxin and may thus be mediated by G-protein-coupled receptors. IL-10 markedly increased CCL2 production induced by CCL16, but suppressed that of CXCL8. It also enhanced the chemotactic response to CCL16. Addition of antibodies blocking CCR1, but not CCR8, prevented this enhanced chemotactic response and suggested that CCR1 is primarily involved. We propose that IL-10 modulates the effects of CCL16 on monocytes by increasing their CCR1-dependent response. The coordinated secretion of CCL16 and IL-10 may thus enhance monocyte infiltration.

Cell Line↗
PubMedDate not supplied

Ly-6A/E gene is widely expressed among transformed nonhematopoietic cells. Autocrine modulation by interferon.

Expression of the Ly-6A/E gene by transformed cells was investigated in 14 cell cultures of C57BL/6 and BALB/c mouse origin derived from spontaneous or chemically-induced non-hematopoietic tumours and from cells transformed by SV40 virus. Histologic types included carcinomas, sarcomas and a melanoma. Thirteen out of 14 cell cultures expressed membrane Ly-6A/E antigens; only the B16-A melanoma was negative, but it expressed Ly-6A/E after incubation with IFN-gamma. The effect of in vitro permanence was studied on early (< 10) and late (> 20) passages of B16-A melanoma and MN/MCA1 fibrosarcoma. Late passage B16-A cells were Ly-6A/E-negative and refractory to induction of Ly-6A/E (but not of H-2 antigens) by IFN-alpha, IFN-beta, or IFN-gamma; MN/MCA1 maintained a high expression of Ly-6A/E, but no increase was induced by IFNs. It was found that both early and late in vitro passages of MN/MCA1 actively produced IFN-alpha/beta. The analysis of cells of fibroblastic origin revealed a significant correlation between IFN release in the culture medium and Ly-6A/E levels. Culture of fibrosarcoma cells in the presence of an anti-IFN-alpha/beta serum reduced Ly-6A/E expression, thus indicating the existence of an autocrine loop.

Animals↗
PubMedDate not supplied

[Macrophage activation and lymphokine production in the mouse by lymphocytes sensitized against Trichomonas vaginalis].

In this study we have examined whether resident peritoneal macrophages could be activated in vitro by immune T lymphocytes obtained from mice which were immunized with live Trichomonas vaginalis (T. vaginalis). T lymphocytes obtained from mice previously sensitized against T. vaginalis, showed a significant proliferative response when cultured in vitro in the presence of T. vaginalis. Resident peritoneal macrophages obtained from untreated syngenic Balb/c mice revealed an increasing cytotoxic activity against the protozoa when seeded with increasing concentrations of purified immune T lymphocytes and a constant number of H3 thymidine-labeled T. vaginalis. This cytotoxicity was detectable after 24 h of culture and peaked after 48 h. Supernatants obtained from cocultures of macrophages, immune T lymphocytes and T. vaginalis contained gamma-Interferon and TNF alpha/beta.

Animals↗
PubMedDate not supplied

[Perilymphatic injection of interleukin-2 (IL-2) in recurrent squamous cell carcinoma of the head and neck].

Twenty patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line, purified by high pressure liquid chromatography for 10 days. Two hundred (ten patients), one thousand (five patients) and five thousand (five patients) units of IL-2 in 0.5 ml were injected 1.5 cm from the point where the sternocleidomastoid muscle inserts itself on the mastoid. Whenever possible, the treatment cycles were repeated at 45 day intervals. In 13 patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. There were non systemic disturbances after injection and only moderate local swelling and pain.

Adult↗
PubMedDate not supplied

Ability of interleukin-4 to elicit an immunoreaction against a murine tumor.

A T cell-derived lymphokine, IL-4, has been shown to have activating and growth promoting properties on macrophages, T cells and B cells. IL-4 could thus be used to augment immunoreactivity in the treatment of tumors. To evaluate its ability to promote an immune reaction capable of hampering tumor growth, we injected mice with small amounts of recombinant IL-4 perilymphatically daily for ten days near the challenge site of a poorly immunogenic syngenic fibrosarcoma (CE-2). These low doses activated such a strong immune reaction that incipient syngenic tumors were rejected. Our results suggest that the host immune system plays a fundamental role in this IL-4 dependent lymphokine-activated tumor inhibition (LATI).

Animals↗
PubMedDate not supplied

[Genetic control of spontaneous resistance to murine adenocarcinoma (ADK-lt)].

The genetic control of spontaneous resistance by virgin mice towards a mammary adenocarcinoma of BALB/c mice origin was studied in F1 hybrid mice produced by crossing BALB/c females with males of different haplotype from BALB, A, or B10 strain. The findings obtained show that the intensity of natural resistance in vivo is not under an unigenic control but is the result of multiple interactions among genes located both inside or outside the major histocompatibility complex.

Adenocarcinoma↗
PubMedDate not supplied

Primary humoral immune response against tumor membrane antigens and foreign antigens by plasma cell tumor bearer mice.

The MOPC-460 plasma cell tumor possesses tumor specific antigens. It nevertheless grows and kills its syngeneic host. The possible impairment of immune responsiveness in tumor bearing mice was investigated by measuring their ability to mount a humoral immune response against foreign antigens, such as sheep red blood cells or bacteriophage T4. No significant decrease in the response to either antigen was found until the tumor mass exceeded 10-15% of the host's body weight. Moreover, circulating anti-tumor antibodies were detected in the serum throughout the initial period of tumor growth. The possible interference of these antibodies with cell-mediated defence mechanism was ruled out by experiments where the humoral response was selectively suppressed from birth by repeated administrations of anti-immunoglobulin heavy chain antiserum. In a "suppressed" mice, tumors took, grew and developed more rapidly than in controls. It is concluded that, at least in the model studied, the humoral immune response operates as a defence mechanism against expansion of the tumor clone.

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