Интерлейкины

Страница: 7/9

1твие на эффективность клеточной защиты. От преобладания того

1или иного из этих цитокинов могут зависеть исход инфекции и эф-

1фективность противоопухолевой защиты. /2461к/

4. Индуцирует продукцию гамма-ИФ Т-лимфоцитами. Усиливает про-

лиферацию лимфоцитов в ответ на митогены. Потенцирует действи-

еИЛ-2. /2460к/95/

- Усиливает действие вакцины против лейшманиоза. /2460к/95/

1Последствия удаления генов цитокинов

1или их рецепторов /2317к/97/

1───────────────────────────────────────────────────────────────

1Цитокин, │ Ожидаемые последствия │ Неожиданные

1рецепторы│ │ последствия

1───────────────────────────────────────────────────────────────

1ИЛ-12 Ослабление образования Тh1

Лечение инфеционных заболеваний. /2356к/

1───────────────────────────────────────────────────────────────

.

ИЛ-13 9- Т-лимфоциты _Противовоспалительный агент

17 (Тх2)

Эффекты:

1. Противовоспалительный агент

_Стимуляция синтеза

- рецепторного антагониста ИЛ-1 (РАИЛ);

_Подавляет образование . провоспалительных цитокинов. По харак-

теру влияния очень близок к ИЛ-4. /2461к/

- ИЛ-1, ИЛ-6,

- ФНО

5Индукция п-ИФ продукции РВ2, Т- и ЕКК ИЛ-6, ИЛ-1, ФНО. - ???

2. Стимулирует пролиферацию _стволовых клеток ., дифференцировку

моноцитов. /2300к/

3. Хемоаттрактор для моноцитов.

4. Ингибирует противопаразитарную активность, токсичность, мак-

рофаг-связанную иммуносупрессию. /2460к/

.

ИЛ-15

Эффекты:

1. Активирует ЕКК, пролиферацию Т-лимфоцитов, их дифференциров-

ку в Тк. /2460к/ Инициирует образование лимфокинактивирован-

ных киллеров. /2460к/95/

───────────────────────────────────────────────────────────────

Примечание: ЭК - эндотелиальные клетки

рэс - ретикулоэндотелиальная система

ФНО - фактор некроза опухолей

ИФ - интерферон

ЕКК - естественные клетки-киллеры

Pg - простагландины

ФАТ - фактор активации тромбоцитов

.

Oppenheimer-Marks N. Brezinschek RI. Mohamadzadeh M. Vita R. Lipsky

PE.

_Interleukin 15 . is produced by endothelial cells and increases the

transendothelial migration of T cells In vitro and in the SCID mouse-human

rheumatoid arthritis model In vivo.

Source

Journal of Clinical Investigation. 101(6):1261-72, 1998 Mar 15.

The capacity of endothelial cells (EC) to produce IL-15 and the capacity

of IL-15 to influence transendothelial migration of T cells was examined.

Human umbilical vein endothelial cells expressed both IL-15 mRNA and

protein. Moreover, endothelial-derived IL-15 enhanced transendothelial

migration of T cells as evidenced by the inhibition of this process by

blocking monoclonal antibodies to IL-15. IL-15 enhanced transendothelial

migration of T cells by activating the binding capacity of the integrin

adhesion molecule LFA-1 (CD11a/CD18) and also increased T cell motility.

In addition, IL-15 induced expression of the early activation molecule

CD69. The importance of IL-15 in regulating migration of T cells in vivo

was documented by its capacity to enhance accumulation of adoptively

transferred human T cells in rheumatoid arthritis synovial tissue

engrafted into immune deficient SCID mice. These results demonstrate that

EC produce IL-15 and imply that endothelial IL-15 plays a critical role in

stimulation of T cells to extravasate into inflammatory tissue.

Lantero S. Sacco O. Scala C. Rossi GA.

Stimulation of blood mononuclear cells of atopic children with the

relevant allergen induces the release of eosinophil chemotaxins such as

_IL-3, IL-5, and GM-CSF.

Journal of Asthma. 34(2):141-52, 1997.

Peripheral blood mononuclear cells (PBMC) from 10 atopic asthmatic

children (atopics), sensitized to Dermatophagoides pteronyssinus (Dp), and

from 5 nonatopic healthy children (controls) were stimulated with Dp

extract or with birch extract (Be). After 6 days we tested the

supernatant's (Sn) chemotactic activity toward purified blood

eosinbnophils and T-lymphocyte proliferation. Dp induced a statistically

significant T-cell proliferation from atopics as compared to controls (p <

0.05), which correlated with the levels of eosinophil chemotactic activity

in the Sn (r = 0.713; p < 0.05). Measurable levels of IL-3, IL-5, and

GM-CSF were demonstrated in the Sn of Dp-stimulated PBMC from atopics,

while eosinophil locomotion toward different concentrations of recombinant

human (rh) IL-3, rhIL-5, and rhGM-CSF confirmed that these cytokines were

able to stimulate eosinophil chemotaxis in a close concentration range.

Preincubation of different concentrations of the same Sn with blocking

antisera demonstrated that anti-human (ah) IL-3, ahIL-5, and ahGM-CSF

effectively decreased eosinophil chemotaxis (p < 0.05; each comparison).

Thus PBMC activation with the relevant allergen induces the release by T

cells with a Th2 phenotype of chemotactic factors for eosinophils.

Ogawa M. Tsutsui T. Zou JP. Mu J. Wijesuriya R. Yu WG. Herrmann S.

Kubo T. Fujiwara H. Hamaoka T.

Enhanced induction of very late antigen 4/lymphocyte function-associated

_antigen 1-dependent T-cell migration to tumor sites following

_administration of interleukin 12.

Cancer Research. 57(11):2216-22, 1997 Jun 1.

Administration of interleukin 12 (IL-12) into mice bearing CSA1M, OV-HM,

Meth A, or MCH-1-A1 tumor induced complete regression of CSA1M and OV-HM

tumors but induced only a slight growth inhibition of Meth A and MCH-1-A1

tumors. These effects of IL-12 were associated with high and only marginal

levels of T-cell infiltration into CSA1M/OV-HM and Meth A/MCH-1-A1 tumor

masses, respectively. Here, we investigated the role of IL-12 in the

induction of T-cell migration. Spleen cells from untreated or

IL-12-treated CSA1M-bearing mice were stained in vitro with a fluorescein

chemical and transferred i.v. into IL-12-untreated CSA1M-bearing mice.

Migration of donor cells was quantitated by counting the number of

fluorescent cells on cryostat sections of tumor masses. Although only a

slight migration was detected for spleen cells from IL-12-untreated

CSA1M-bearing as well as IL-12-treated or untreated normal mice, enhanced

migration was observed for cells from IL-12-treated CSA1M-bearing mice. A

similar enhanced migration was observed for the OV-HM model. In contrast,

such an enhancement was only marginal in the Meth A and MCH-1-A1 models.

Immunohistochemical studies of tumors from IL-12-treated mice revealed

that the predominant T-cell subset was CD4+ in CSA1M and CD8+ in OV-HM

tumor masses. Consistent with this observation, the dominant subset of

migrating T cells was found to be CD4+ in the CSA1M and CD8+ in the OV-HM

models. T-cell migration was inhibited by pretreatment of recipients with

either combination of anti-very late antigen 4 + anti-vascular cell

adhesion molecule 1 or anti-lymphocyte function-associated antigen 1 +

anti-intercellular adhesion molecule 1 monoclonal antibody. These results

indicate that IL-12 can confer T cells with a capacity to migrate to tumor

sites through very late antigen 4/lymphocyte function-associated antigen 1

adhesion pathways and that the in vivo acquisition of such a capacity

following IL-12 treatment correlates with the induction of tumor

regression.

Marth T. Strober W. Seder RA. Kelsall BL.

Regulation of transforming growth factor-beta production by

Реферат опубликован: 11/04/2005 (18298 прочтено)